Incidental Mutation 'R6353:Smarca4'
| ID |
512300 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Smarca4
|
| Ensembl Gene |
ENSMUSG00000032187 |
| Gene Name |
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 |
| Synonyms |
SW1/SNF, Brg1, SNF2beta, b2b692Clo, b2b508.1Clo |
| MMRRC Submission |
044505-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R6353 (G1)
|
| Quality Score |
169.009 |
|
Status
|
Not validated
|
| Chromosome |
9 |
| Chromosomal Location |
21527465-21615526 bp(+) (GRCm39) |
| Type of Mutation |
critical splice donor site (2 bp from exon) |
| DNA Base Change (assembly) |
T to A
at 21590445 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000133922
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034707]
[ENSMUST00000098948]
[ENSMUST00000174008]
|
| AlphaFold |
Q3TKT4 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000034707
|
| SMART Domains |
Protein: ENSMUSP00000034707
Gene: ENSMUSG00000032187
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
6 |
58 |
N/A |
INTRINSIC |
|
low complexity region
|
130 |
153 |
N/A |
INTRINSIC |
|
QLQ
|
170 |
206 |
3.98e-14 |
SMART |
|
low complexity region
|
221 |
247 |
N/A |
INTRINSIC |
|
low complexity region
|
252 |
289 |
N/A |
INTRINSIC |
|
low complexity region
|
304 |
330 |
N/A |
INTRINSIC |
|
low complexity region
|
407 |
418 |
N/A |
INTRINSIC |
|
HSA
|
460 |
532 |
2e-27 |
SMART |
|
coiled coil region
|
563 |
595 |
N/A |
INTRINSIC |
|
BRK
|
612 |
656 |
5.17e-21 |
SMART |
|
low complexity region
|
657 |
672 |
N/A |
INTRINSIC |
|
low complexity region
|
691 |
702 |
N/A |
INTRINSIC |
|
DEXDc
|
750 |
942 |
5.17e-38 |
SMART |
|
Blast:DEXDc
|
953 |
985 |
7e-10 |
BLAST |
|
low complexity region
|
1019 |
1034 |
N/A |
INTRINSIC |
|
HELICc
|
1110 |
1194 |
7.27e-24 |
SMART |
|
low complexity region
|
1252 |
1267 |
N/A |
INTRINSIC |
|
SnAC
|
1288 |
1356 |
2.8e-29 |
SMART |
|
low complexity region
|
1360 |
1385 |
N/A |
INTRINSIC |
|
low complexity region
|
1388 |
1398 |
N/A |
INTRINSIC |
|
BROMO
|
1422 |
1533 |
4.19e-42 |
SMART |
|
low complexity region
|
1534 |
1557 |
N/A |
INTRINSIC |
|
low complexity region
|
1578 |
1588 |
N/A |
INTRINSIC |
|
low complexity region
|
1594 |
1614 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000098948
|
| SMART Domains |
Protein: ENSMUSP00000096547
Gene: ENSMUSG00000032187
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
6 |
58 |
N/A |
INTRINSIC |
|
low complexity region
|
130 |
153 |
N/A |
INTRINSIC |
|
QLQ
|
170 |
206 |
3.98e-14 |
SMART |
|
low complexity region
|
221 |
247 |
N/A |
INTRINSIC |
|
low complexity region
|
252 |
289 |
N/A |
INTRINSIC |
|
low complexity region
|
304 |
330 |
N/A |
INTRINSIC |
|
low complexity region
|
407 |
418 |
N/A |
INTRINSIC |
|
HSA
|
460 |
532 |
2e-27 |
SMART |
|
coiled coil region
|
563 |
595 |
N/A |
INTRINSIC |
|
BRK
|
612 |
656 |
5.17e-21 |
SMART |
|
low complexity region
|
657 |
672 |
N/A |
INTRINSIC |
|
low complexity region
|
691 |
702 |
N/A |
INTRINSIC |
|
DEXDc
|
750 |
942 |
5.17e-38 |
SMART |
|
Blast:DEXDc
|
953 |
985 |
7e-10 |
BLAST |
|
low complexity region
|
1019 |
1034 |
N/A |
INTRINSIC |
|
HELICc
|
1110 |
1194 |
7.27e-24 |
SMART |
|
low complexity region
|
1252 |
1267 |
N/A |
INTRINSIC |
|
SnAC
|
1288 |
1356 |
2.8e-29 |
SMART |
|
low complexity region
|
1363 |
1388 |
N/A |
INTRINSIC |
|
low complexity region
|
1391 |
1401 |
N/A |
INTRINSIC |
|
BROMO
|
1425 |
1536 |
4.19e-42 |
SMART |
|
low complexity region
|
1537 |
1560 |
N/A |
INTRINSIC |
|
low complexity region
|
1581 |
1591 |
N/A |
INTRINSIC |
|
low complexity region
|
1597 |
1617 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000172996
|
| SMART Domains |
Protein: ENSMUSP00000133535
Gene: ENSMUSG00000032187
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
26 |
52 |
N/A |
INTRINSIC |
|
low complexity region
|
57 |
94 |
N/A |
INTRINSIC |
|
low complexity region
|
109 |
135 |
N/A |
INTRINSIC |
|
low complexity region
|
212 |
223 |
N/A |
INTRINSIC |
|
HSA
|
265 |
337 |
2e-27 |
SMART |
|
coiled coil region
|
367 |
399 |
N/A |
INTRINSIC |
|
BRK
|
417 |
461 |
5.17e-21 |
SMART |
|
low complexity region
|
462 |
477 |
N/A |
INTRINSIC |
|
low complexity region
|
496 |
507 |
N/A |
INTRINSIC |
|
DEXDc
|
555 |
747 |
5.17e-38 |
SMART |
|
Blast:DEXDc
|
758 |
790 |
6e-10 |
BLAST |
|
low complexity region
|
824 |
839 |
N/A |
INTRINSIC |
|
HELICc
|
915 |
999 |
7.27e-24 |
SMART |
|
low complexity region
|
1088 |
1105 |
N/A |
INTRINSIC |
|
SnAC
|
1126 |
1194 |
2.8e-29 |
SMART |
|
low complexity region
|
1201 |
1226 |
N/A |
INTRINSIC |
|
low complexity region
|
1229 |
1239 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000174008
|
| SMART Domains |
Protein: ENSMUSP00000133922
Gene: ENSMUSG00000032187
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
6 |
58 |
N/A |
INTRINSIC |
|
low complexity region
|
130 |
153 |
N/A |
INTRINSIC |
|
QLQ
|
170 |
206 |
3.98e-14 |
SMART |
|
low complexity region
|
221 |
247 |
N/A |
INTRINSIC |
|
low complexity region
|
252 |
289 |
N/A |
INTRINSIC |
|
low complexity region
|
304 |
330 |
N/A |
INTRINSIC |
|
low complexity region
|
407 |
418 |
N/A |
INTRINSIC |
|
HSA
|
460 |
532 |
2e-27 |
SMART |
|
coiled coil region
|
563 |
595 |
N/A |
INTRINSIC |
|
BRK
|
612 |
656 |
5.17e-21 |
SMART |
|
low complexity region
|
657 |
672 |
N/A |
INTRINSIC |
|
low complexity region
|
691 |
702 |
N/A |
INTRINSIC |
|
DEXDc
|
750 |
942 |
5.17e-38 |
SMART |
|
Blast:DEXDc
|
953 |
985 |
7e-10 |
BLAST |
|
low complexity region
|
1019 |
1034 |
N/A |
INTRINSIC |
|
HELICc
|
1110 |
1194 |
7.27e-24 |
SMART |
|
low complexity region
|
1252 |
1267 |
N/A |
INTRINSIC |
|
SnAC
|
1288 |
1356 |
2.8e-29 |
SMART |
|
low complexity region
|
1360 |
1385 |
N/A |
INTRINSIC |
|
low complexity region
|
1388 |
1398 |
N/A |
INTRINSIC |
|
BROMO
|
1422 |
1532 |
1.36e-41 |
SMART |
|
low complexity region
|
1533 |
1556 |
N/A |
INTRINSIC |
|
low complexity region
|
1577 |
1587 |
N/A |
INTRINSIC |
|
low complexity region
|
1593 |
1613 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000184017
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.8%
- 20x: 93.3%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
PHENOTYPE: Homozygotes for a null allele die in utero before implantation. Embryos heterozygous for this null allele and an ENU-induced allele show impaired definitive erythropoiesis, anemia and lethality during organogenesis. Heterozygotes for a different null allele show cyanosis and cardiovascular defects. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 41 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930550C14Rik |
C |
A |
9: 53,325,642 (GRCm39) |
Q60K |
probably benign |
Het |
| Aadacl2fm2 |
A |
T |
3: 59,659,529 (GRCm39) |
L327F |
probably damaging |
Het |
| Aamp |
T |
C |
1: 74,319,987 (GRCm39) |
D397G |
probably benign |
Het |
| Aco1 |
G |
A |
4: 40,186,367 (GRCm39) |
R593Q |
probably benign |
Het |
| Acta1 |
T |
C |
8: 124,620,426 (GRCm39) |
E4G |
probably benign |
Het |
| Apob |
A |
T |
12: 8,059,421 (GRCm39) |
K2601N |
probably damaging |
Het |
| Arpin |
C |
A |
7: 79,585,093 (GRCm39) |
|
probably benign |
Het |
| Asnsd1 |
T |
C |
1: 53,386,938 (GRCm39) |
I230V |
probably benign |
Het |
| Baiap2l1 |
C |
T |
5: 144,218,898 (GRCm39) |
E237K |
possibly damaging |
Het |
| Chek1 |
T |
C |
9: 36,635,255 (GRCm39) |
K43E |
probably benign |
Het |
| Clec2g |
T |
A |
6: 128,959,895 (GRCm39) |
|
probably null |
Het |
| Cnot10 |
A |
G |
9: 114,426,614 (GRCm39) |
L646P |
probably damaging |
Het |
| Cyp2j9 |
T |
C |
4: 96,474,135 (GRCm39) |
T102A |
probably benign |
Het |
| Dnase1l2 |
A |
T |
17: 24,661,219 (GRCm39) |
L30Q |
probably damaging |
Het |
| Edc3 |
T |
C |
9: 57,623,520 (GRCm39) |
S152P |
probably benign |
Het |
| Gask1b |
A |
T |
3: 79,848,647 (GRCm39) |
R464S |
probably damaging |
Het |
| Gpr160 |
A |
T |
3: 30,950,171 (GRCm39) |
D81V |
probably damaging |
Het |
| Intu |
A |
T |
3: 40,608,138 (GRCm39) |
D32V |
probably damaging |
Het |
| Itga5 |
T |
C |
15: 103,260,950 (GRCm39) |
E512G |
probably damaging |
Het |
| Khnyn |
T |
C |
14: 56,131,760 (GRCm39) |
F561L |
possibly damaging |
Het |
| Kmt2e |
T |
A |
5: 23,698,243 (GRCm39) |
V645E |
probably damaging |
Het |
| Mcoln3 |
T |
C |
3: 145,836,909 (GRCm39) |
F247S |
probably damaging |
Het |
| Nek9 |
G |
A |
12: 85,348,603 (GRCm39) |
T977I |
probably damaging |
Het |
| Nphs1 |
A |
G |
7: 30,173,969 (GRCm39) |
T1015A |
probably damaging |
Het |
| Ntmt2 |
A |
G |
1: 163,531,680 (GRCm39) |
Y158H |
possibly damaging |
Het |
| Nudcd1 |
T |
C |
15: 44,284,158 (GRCm39) |
Y76C |
probably damaging |
Het |
| Or2a54 |
C |
A |
6: 43,093,070 (GRCm39) |
Y131* |
probably null |
Het |
| Or8b44 |
T |
C |
9: 38,410,112 (GRCm39) |
I49T |
probably benign |
Het |
| Pgd |
C |
T |
4: 149,245,209 (GRCm39) |
|
probably null |
Het |
| Prl7c1 |
A |
G |
13: 27,957,709 (GRCm39) |
S244P |
possibly damaging |
Het |
| Rpap1 |
G |
T |
2: 119,607,377 (GRCm39) |
|
probably null |
Het |
| Rrp8 |
G |
A |
7: 105,383,325 (GRCm39) |
R314* |
probably null |
Het |
| Stambpl1 |
A |
G |
19: 34,211,520 (GRCm39) |
|
probably null |
Het |
| Tmeff2 |
T |
C |
1: 51,220,985 (GRCm39) |
V320A |
probably damaging |
Het |
| Top2b |
A |
G |
14: 16,416,671 (GRCm38) |
K83E |
probably damaging |
Het |
| Ttc39b |
C |
G |
4: 83,148,730 (GRCm39) |
V560L |
probably benign |
Het |
| Ttn |
A |
T |
2: 76,672,153 (GRCm39) |
|
probably benign |
Het |
| Usp32 |
T |
C |
11: 84,913,107 (GRCm39) |
I934V |
probably benign |
Het |
| Uxs1 |
T |
C |
1: 43,836,410 (GRCm39) |
I122V |
probably damaging |
Het |
| Vmn1r168 |
A |
G |
7: 23,240,944 (GRCm39) |
N267S |
probably benign |
Het |
| Vmn2r16 |
A |
G |
5: 109,488,119 (GRCm39) |
N331D |
probably benign |
Het |
|
| Other mutations in Smarca4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01380:Smarca4
|
APN |
9 |
21,590,369 (GRCm39) |
missense |
probably benign |
0.30 |
|
IGL01694:Smarca4
|
APN |
9 |
21,577,166 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02147:Smarca4
|
APN |
9 |
21,546,999 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL02417:Smarca4
|
APN |
9 |
21,612,386 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02421:Smarca4
|
APN |
9 |
21,550,535 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02550:Smarca4
|
APN |
9 |
21,597,418 (GRCm39) |
missense |
probably benign |
0.25 |
|
IGL02794:Smarca4
|
APN |
9 |
21,584,638 (GRCm39) |
splice site |
probably benign |
|
|
IGL03030:Smarca4
|
APN |
9 |
21,547,132 (GRCm39) |
missense |
probably benign |
0.14 |
|
IGL03037:Smarca4
|
APN |
9 |
21,544,231 (GRCm39) |
unclassified |
probably benign |
|
|
IGL03069:Smarca4
|
APN |
9 |
21,547,132 (GRCm39) |
missense |
probably benign |
0.14 |
|
IGL03355:Smarca4
|
APN |
9 |
21,547,132 (GRCm39) |
missense |
probably benign |
0.14 |
|
R0123:Smarca4
|
UTSW |
9 |
21,548,620 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0134:Smarca4
|
UTSW |
9 |
21,548,620 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0230:Smarca4
|
UTSW |
9 |
21,612,168 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0269:Smarca4
|
UTSW |
9 |
21,547,497 (GRCm39) |
missense |
probably benign |
0.09 |
|
R0631:Smarca4
|
UTSW |
9 |
21,570,280 (GRCm39) |
splice site |
probably benign |
|
|
R0665:Smarca4
|
UTSW |
9 |
21,612,239 (GRCm39) |
small deletion |
probably benign |
|
|
R0726:Smarca4
|
UTSW |
9 |
21,611,435 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0801:Smarca4
|
UTSW |
9 |
21,553,850 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R0918:Smarca4
|
UTSW |
9 |
21,547,511 (GRCm39) |
missense |
probably benign |
0.16 |
|
R1411:Smarca4
|
UTSW |
9 |
21,570,251 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1604:Smarca4
|
UTSW |
9 |
21,612,239 (GRCm39) |
small deletion |
probably benign |
|
|
R1768:Smarca4
|
UTSW |
9 |
21,612,479 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R2004:Smarca4
|
UTSW |
9 |
21,588,776 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2031:Smarca4
|
UTSW |
9 |
21,597,358 (GRCm39) |
missense |
possibly damaging |
0.68 |
|
R2211:Smarca4
|
UTSW |
9 |
21,597,325 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2512:Smarca4
|
UTSW |
9 |
21,546,994 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R2875:Smarca4
|
UTSW |
9 |
21,553,876 (GRCm39) |
missense |
possibly damaging |
0.55 |
|
R3786:Smarca4
|
UTSW |
9 |
21,583,355 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R4829:Smarca4
|
UTSW |
9 |
21,550,623 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R5084:Smarca4
|
UTSW |
9 |
21,572,059 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5222:Smarca4
|
UTSW |
9 |
21,567,002 (GRCm39) |
missense |
probably benign |
0.01 |
|
R5785:Smarca4
|
UTSW |
9 |
21,597,322 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5844:Smarca4
|
UTSW |
9 |
21,589,238 (GRCm39) |
intron |
probably benign |
|
|
R5964:Smarca4
|
UTSW |
9 |
21,558,726 (GRCm39) |
missense |
probably benign |
0.00 |
|
R6001:Smarca4
|
UTSW |
9 |
21,544,205 (GRCm39) |
unclassified |
probably benign |
|
|
R6072:Smarca4
|
UTSW |
9 |
21,611,417 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6254:Smarca4
|
UTSW |
9 |
21,611,173 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6320:Smarca4
|
UTSW |
9 |
21,548,671 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6461:Smarca4
|
UTSW |
9 |
21,590,316 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6886:Smarca4
|
UTSW |
9 |
21,570,127 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7098:Smarca4
|
UTSW |
9 |
21,546,116 (GRCm39) |
missense |
probably benign |
0.10 |
|
R7253:Smarca4
|
UTSW |
9 |
21,570,256 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7307:Smarca4
|
UTSW |
9 |
21,550,096 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7382:Smarca4
|
UTSW |
9 |
21,570,229 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7445:Smarca4
|
UTSW |
9 |
21,597,543 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7535:Smarca4
|
UTSW |
9 |
21,558,921 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R7573:Smarca4
|
UTSW |
9 |
21,550,371 (GRCm39) |
splice site |
probably null |
|
|
R7644:Smarca4
|
UTSW |
9 |
21,566,950 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7734:Smarca4
|
UTSW |
9 |
21,578,658 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R7833:Smarca4
|
UTSW |
9 |
21,558,655 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R8085:Smarca4
|
UTSW |
9 |
21,570,108 (GRCm39) |
splice site |
probably null |
|
|
R8119:Smarca4
|
UTSW |
9 |
21,558,922 (GRCm39) |
missense |
possibly damaging |
0.61 |
|
R8320:Smarca4
|
UTSW |
9 |
21,588,798 (GRCm39) |
missense |
probably benign |
0.10 |
|
R8445:Smarca4
|
UTSW |
9 |
21,612,239 (GRCm39) |
small deletion |
probably benign |
|
|
R8493:Smarca4
|
UTSW |
9 |
21,570,144 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8748:Smarca4
|
UTSW |
9 |
21,546,164 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
R8788:Smarca4
|
UTSW |
9 |
21,550,024 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8817:Smarca4
|
UTSW |
9 |
21,547,497 (GRCm39) |
missense |
probably benign |
0.04 |
|
R9241:Smarca4
|
UTSW |
9 |
21,550,604 (GRCm39) |
missense |
possibly damaging |
0.72 |
|
R9446:Smarca4
|
UTSW |
9 |
21,547,155 (GRCm39) |
missense |
unknown |
|
|
R9570:Smarca4
|
UTSW |
9 |
21,580,849 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9727:Smarca4
|
UTSW |
9 |
21,611,160 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9801:Smarca4
|
UTSW |
9 |
21,586,397 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Smarca4
|
UTSW |
9 |
21,614,253 (GRCm39) |
nonsense |
probably null |
|
|
| Predicted Primers |
PCR Primer
(F):5'- ATAGCGCATGGACTTGGACC -3'
(R):5'- TCTTGTGACAGCTATAGAGGTAGG -3'
Sequencing Primer
(F):5'- GCGTGAAGAAGCCCGCAAC -3'
(R):5'- GAGGTAGGAACTAAACATCCCTACG -3'
|
| Posted On |
2018-04-27 |
Incidental Mutation