Mutagenetix > Incidental Mutation

Incidental Mutation 'R1795:Dnmt3b'

202106

Institutional Source

Beutler Lab

Gene Symbol

Dnmt3b

Ensembl Gene

ENSMUSG00000027478

Gene Name

DNA methyltransferase 3B

Synonyms

MMRRC Submission

039825-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1795 (G1)

Quality Score

176

Status

Not validated

Chromosome

Chromosomal Location

153491370-153529650 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 153525559 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Lysine at position 741 (E741K)

Ref Sequence

ENSEMBL: ENSMUSP00000105395 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056495] [ENSMUST00000072997] [ENSMUST00000081628] [ENSMUST00000088976] [ENSMUST00000103150] [ENSMUST00000103151] [ENSMUST00000109771] [ENSMUST00000109774] [ENSMUST00000109773] [ENSMUST00000109772]

AlphaFold

O88509

PDB Structure

Crystal Structure of the PWWP Domain of Mammalian DNA Methyltransferase Dnmt3b [X-RAY DIFFRACTION]

Predicted Effect

probably benign
Transcript: ENSMUST00000056495
AA Change: E762K

PolyPhen 2 Score 0.198 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000051830
Gene: ENSMUSG00000027478
AA Change: E762K

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	582	732	3.1e-15	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000072997
AA Change: E761K

PolyPhen 2 Score 0.579 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000072761
Gene: ENSMUSG00000027478
AA Change: E761K

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	581	731	4.5e-15	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000081628
AA Change: E741K

PolyPhen 2 Score 0.924 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000080334
Gene: ENSMUSG00000027478
AA Change: E741K

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	1e-54	PDB
Blast:RING	463	512	7e-28	BLAST
Pfam:DNA_methylase	561	711	4.4e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000088976

SMART Domains

Protein: ENSMUSP00000086370
Gene: ENSMUSG00000027478

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	7e-55	PDB
Blast:RING	483	532	5e-28	BLAST
Pfam:DNA_methylase	581	727	2.9e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000103150

SMART Domains

Protein: ENSMUSP00000099439
Gene: ENSMUSG00000027478

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	8e-55	PDB
Blast:RING	463	512	6e-28	BLAST
Pfam:DNA_methylase	561	707	4.2e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000103151

SMART Domains

Protein: ENSMUSP00000099440
Gene: ENSMUSG00000027478

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	8e-55	PDB
Blast:RING	463	512	6e-28	BLAST
Pfam:DNA_methylase	561	707	4.2e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000109771
AA Change: E762K

PolyPhen 2 Score 0.198 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000105393
Gene: ENSMUSG00000027478
AA Change: E762K

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	582	732	3.1e-15	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000109774
AA Change: E761K

PolyPhen 2 Score 0.579 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000105396
Gene: ENSMUSG00000027478
AA Change: E761K

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	581	731	4.5e-15	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000109773
AA Change: E741K

PolyPhen 2 Score 0.924 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000105395
Gene: ENSMUSG00000027478
AA Change: E741K

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	1e-54	PDB
Blast:RING	463	512	7e-28	BLAST
Pfam:DNA_methylase	561	711	4.4e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000109772

SMART Domains

Protein: ENSMUSP00000105394
Gene: ENSMUSG00000027478

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	7e-55	PDB
Blast:RING	483	532	5e-28	BLAST
Pfam:DNA_methylase	581	727	2.9e-15	PFAM

Coding Region Coverage

1x: 97.5%
3x: 96.9%
10x: 95.4%
20x: 92.6%

Validation Efficiency

MGI Phenotype

FUNCTION: This is one of two related genes encoding de novo DNA methyltransferases, which are responsible for the establishment of DNA methylation patterns in embryos. Loss of function of this gene results in severe developmental defects and loss of viability. Mutation of the related gene in humans causes immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. There is a pseudogene for this gene located adjacent to this gene in the same region of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Nov 2012]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit growth retardation and rostral neural tube defects, and die prenatally. Mutants exhibit slight under-methylation of endogenous viral DNA and substantial demethylation of minor satellite DNA. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8a	A	G	11: 109,941,792 (GRCm39)	I1159T	probably benign	Het
Abcc1	T	C	16: 14,283,001 (GRCm39)	V1159A	possibly damaging	Het
Abcg5	A	G	17: 84,981,007 (GRCm39)	I194T	probably damaging	Het
Abtb2	A	G	2: 103,397,369 (GRCm39)	T100A	probably benign	Het
Adam4	C	T	12: 81,468,068 (GRCm39)	M184I	probably benign	Het
Afap1l2	T	C	19: 56,916,841 (GRCm39)	D155G	probably damaging	Het
Ahnak	T	C	19: 8,979,802 (GRCm39)	V362A	possibly damaging	Het
Ak7	C	T	12: 105,692,482 (GRCm39)	R179*	probably null	Het
Akap8	C	A	17: 32,534,451 (GRCm39)	G332C	probably damaging	Het
Akr1e1	T	A	13: 4,645,071 (GRCm39)	Q204L	probably damaging	Het
Ankrd12	T	C	17: 66,293,222 (GRCm39)	E737G	possibly damaging	Het
Atrn	A	G	2: 130,814,208 (GRCm39)	D718G	probably benign	Het
Bco2	A	G	9: 50,452,469 (GRCm39)	S200P	possibly damaging	Het
C030005K15Rik	A	T	10: 97,561,648 (GRCm39)	S28T	unknown	Het
Cdc14a	T	A	3: 116,092,122 (GRCm39)	Q356L	possibly damaging	Het
Cdk5rap3	A	G	11: 96,799,654 (GRCm39)	L387P	probably damaging	Het
Celsr1	A	T	15: 85,914,524 (GRCm39)	S1150T	probably damaging	Het
Cntfr	A	G	4: 41,670,841 (GRCm39)		probably null	Het
Cramp1	T	C	17: 25,183,884 (GRCm39)	N1244D	probably damaging	Het
Csmd3	G	T	15: 47,721,316 (GRCm39)	D1542E	possibly damaging	Het
Cyp4f17	A	T	17: 32,736,943 (GRCm39)	I92F	probably benign	Het
Dhx30	A	T	9: 109,937,051 (GRCm39)		probably null	Het
Dlg1	T	A	16: 31,561,965 (GRCm39)	H120Q	probably benign	Het
Dmgdh	A	T	13: 93,843,207 (GRCm39)	M348L	probably benign	Het
Dock3	T	G	9: 106,902,534 (GRCm39)	H292P	probably damaging	Het
Ercc6	T	A	14: 32,238,985 (GRCm39)	N24K	probably benign	Het
Esco2	T	C	14: 66,064,726 (GRCm39)	Q338R	probably benign	Het
Etl4	T	C	2: 20,812,837 (GRCm39)		probably null	Het
Exoc7	A	T	11: 116,183,347 (GRCm39)	I498N	probably damaging	Het
Fap	G	A	2: 62,378,933 (GRCm39)	S123L	probably damaging	Het
Foxn1	T	C	11: 78,262,051 (GRCm39)	E106G	probably benign	Het
Fscb	T	A	12: 64,521,175 (GRCm39)	D97V	probably damaging	Het
Gabrg1	T	C	5: 70,939,596 (GRCm39)	T174A	possibly damaging	Het
Gan	C	T	8: 117,923,199 (GRCm39)	A461V	possibly damaging	Het
Gbp2	T	A	3: 142,336,284 (GRCm39)	D211E	possibly damaging	Het
Gm10271	A	T	10: 116,792,746 (GRCm39)	Y47N	unknown	Het
Gm17333	G	T	16: 77,649,711 (GRCm39)		noncoding transcript	Het
Gm1758	T	A	16: 14,320,142 (GRCm39)		noncoding transcript	Het
Golga3	A	G	5: 110,355,493 (GRCm39)	K989R	possibly damaging	Het
Gucy2g	C	A	19: 55,187,973 (GRCm39)	V1041F	probably damaging	Het
Guk1	A	T	11: 59,077,639 (GRCm39)	F25I	probably benign	Het
H2al1o	C	T	X: 9,438,329 (GRCm39)	E87K	possibly damaging	Het
Hemgn	C	A	4: 46,395,958 (GRCm39)	C426F	probably damaging	Het
Hps3	A	G	3: 20,066,859 (GRCm39)		probably null	Het
Il2rb	A	T	15: 78,368,187 (GRCm39)	D287E	probably damaging	Het
Ino80	A	T	2: 119,237,340 (GRCm39)	V1123D	probably damaging	Het
Kdm2b	A	G	5: 123,122,523 (GRCm39)		probably null	Het
Kif21a	A	T	15: 90,856,930 (GRCm39)		probably null	Het
Klhl33	A	T	14: 51,129,583 (GRCm39)	N347K	probably damaging	Het
Krt1c	A	G	15: 101,724,861 (GRCm39)	F250L	possibly damaging	Het
Krt82	T	A	15: 101,451,819 (GRCm39)	N332I	possibly damaging	Het
Lgi1	A	G	19: 38,294,631 (GRCm39)	I444V	probably benign	Het
Lmod1	G	A	1: 135,252,862 (GRCm39)	V39M	probably damaging	Het
Lonrf2	G	A	1: 38,852,357 (GRCm39)	P165S	probably benign	Het
Mex3d	T	C	10: 80,217,376 (GRCm39)	T149A	probably benign	Het
Mideas	A	G	12: 84,205,748 (GRCm39)		probably null	Het
Mlxipl	A	C	5: 135,136,024 (GRCm39)	D83A	probably damaging	Het
Mroh8	T	A	2: 157,111,471 (GRCm39)	E161V	probably benign	Het
Mroh9	G	A	1: 162,884,347 (GRCm39)	T397I	probably damaging	Het
Mtss1	T	C	15: 58,930,249 (GRCm39)	D32G	possibly damaging	Het
Mus81	T	C	19: 5,533,504 (GRCm39)	D495G	probably benign	Het
Neurod1	A	C	2: 79,284,673 (GRCm39)	S237A	probably benign	Het
Npas1	G	A	7: 16,208,725 (GRCm39)	R51C	probably damaging	Het
Or11g27	T	C	14: 50,771,159 (GRCm39)	S97P	possibly damaging	Het
P2ry14	T	C	3: 59,023,274 (GRCm39)	N62S	probably damaging	Het
Pcdh15	A	G	10: 74,460,087 (GRCm39)	Y1308C	probably damaging	Het
Pcdhb14	A	T	18: 37,582,588 (GRCm39)	M565L	probably benign	Het
Pde6a	A	G	18: 61,390,283 (GRCm39)	E502G	probably damaging	Het
Pde8b	A	G	13: 95,178,527 (GRCm39)	V566A	probably benign	Het
Phf11b	G	T	14: 59,565,554 (GRCm39)	Q108K	probably benign	Het
Pikfyve	T	C	1: 65,291,716 (GRCm39)	Y1312H	probably damaging	Het
Plcb3	T	C	19: 6,933,381 (GRCm39)		probably benign	Het
Plxna2	G	A	1: 194,488,611 (GRCm39)	G1629D	probably damaging	Het
Plxnb1	T	C	9: 108,929,813 (GRCm39)	V223A	probably benign	Het
Prkca	A	T	11: 107,903,518 (GRCm39)	Y285N	possibly damaging	Het
Prl2a1	A	T	13: 27,992,554 (GRCm39)	N226I	probably damaging	Het
Pus7	A	C	5: 23,946,914 (GRCm39)	M636R	probably damaging	Het
Samd9l	G	A	6: 3,375,264 (GRCm39)	Q666*	probably null	Het
Sema3d	A	G	5: 12,634,854 (GRCm39)	D640G	probably benign	Het
Slc6a15	A	G	10: 103,236,121 (GRCm39)	I279V	probably benign	Het
Slk	T	C	19: 47,608,973 (GRCm39)	V642A	possibly damaging	Het
Spata31e2	C	A	1: 26,722,070 (GRCm39)	G1037*	probably null	Het
Spta1	T	A	1: 174,073,296 (GRCm39)	M2305K	probably damaging	Het
Srrt	T	C	5: 137,301,274 (GRCm39)		probably benign	Het
Stfa2l1	A	T	16: 35,977,228 (GRCm39)	I8L	probably benign	Het
Tap1	T	C	17: 34,413,899 (GRCm39)	L638P	probably benign	Het
Tbccd1	A	T	16: 22,640,995 (GRCm39)	L461M	probably benign	Het
Tecta	T	C	9: 42,289,345 (GRCm39)	T407A	probably benign	Het
Tmbim7	T	C	5: 3,707,493 (GRCm39)		probably null	Het
Tnrc18	C	A	5: 142,800,869 (GRCm39)	V30L	probably benign	Het
Tomm7	A	G	5: 24,049,025 (GRCm39)	F16S	probably damaging	Het
Ugt2a2	A	G	5: 87,622,315 (GRCm39)	S428P	probably benign	Het
Vmn1r189	T	C	13: 22,286,324 (GRCm39)	E171G	probably benign	Het
Vmn1r61	T	C	7: 5,614,324 (GRCm39)		probably benign	Het
Vmn2r120	A	T	17: 57,832,038 (GRCm39)	S250R	probably benign	Het
Vmn2r8	T	C	5: 108,950,972 (GRCm39)	R158G	probably benign	Het
Vmn2r98	A	T	17: 19,286,702 (GRCm39)	Y400F	probably damaging	Het
Vps13c	C	A	9: 67,801,267 (GRCm39)	Y582*	probably null	Het
Zfp518a	T	A	19: 40,904,000 (GRCm39)	F1310I	probably benign	Het
Zswim1	A	G	2: 164,667,320 (GRCm39)	I191V	probably benign	Het

Other mutations in Dnmt3b

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00793:Dnmt3b	APN	2	153,514,422 (GRCm39)	missense	possibly damaging	0.88
IGL00931:Dnmt3b	APN	2	153,528,170 (GRCm39)	splice site	probably benign
IGL01073:Dnmt3b	APN	2	153,512,762 (GRCm39)	splice site	probably benign
IGL01138:Dnmt3b	APN	2	153,503,361 (GRCm39)	missense	probably benign	0.01
IGL01960:Dnmt3b	APN	2	153,518,631 (GRCm39)	missense	possibly damaging	0.83
IGL02884:Dnmt3b	APN	2	153,516,297 (GRCm39)	missense	probably damaging	1.00
IGL03382:Dnmt3b	APN	2	153,528,279 (GRCm39)	missense	probably damaging	1.00
PIT4151001:Dnmt3b	UTSW	2	153,526,399 (GRCm39)	critical splice donor site	probably null
R0062:Dnmt3b	UTSW	2	153,514,192 (GRCm39)	missense	probably benign	0.01
R0122:Dnmt3b	UTSW	2	153,518,618 (GRCm39)	missense	probably damaging	1.00
R0147:Dnmt3b	UTSW	2	153,503,377 (GRCm39)	missense	possibly damaging	0.68
R0178:Dnmt3b	UTSW	2	153,516,938 (GRCm39)	missense	probably benign	0.41
R0751:Dnmt3b	UTSW	2	153,516,762 (GRCm39)	splice site	probably null
R1696:Dnmt3b	UTSW	2	153,518,630 (GRCm39)	nonsense	probably null
R1889:Dnmt3b	UTSW	2	153,518,679 (GRCm39)	missense	probably benign
R2898:Dnmt3b	UTSW	2	153,509,550 (GRCm39)	missense	possibly damaging	0.85
R4201:Dnmt3b	UTSW	2	153,512,337 (GRCm39)	nonsense	probably null
R4630:Dnmt3b	UTSW	2	153,512,235 (GRCm39)	nonsense	probably null
R4870:Dnmt3b	UTSW	2	153,512,284 (GRCm39)	missense	probably benign	0.01
R5648:Dnmt3b	UTSW	2	153,519,118 (GRCm39)	missense	probably damaging	1.00
R5814:Dnmt3b	UTSW	2	153,514,417 (GRCm39)	missense	probably benign	0.00
R6311:Dnmt3b	UTSW	2	153,515,925 (GRCm39)	missense	probably damaging	1.00
R6625:Dnmt3b	UTSW	2	153,507,233 (GRCm39)	missense	probably benign
R6818:Dnmt3b	UTSW	2	153,528,204 (GRCm39)	missense	probably damaging	1.00
R7258:Dnmt3b	UTSW	2	153,525,519 (GRCm39)	splice site	probably null
R7473:Dnmt3b	UTSW	2	153,526,370 (GRCm39)	missense	probably damaging	1.00
R7570:Dnmt3b	UTSW	2	153,518,619 (GRCm39)	missense	probably damaging	1.00
R7627:Dnmt3b	UTSW	2	153,519,500 (GRCm39)	missense	probably benign	0.03
R7709:Dnmt3b	UTSW	2	153,514,140 (GRCm39)	missense	probably benign	0.10
R8483:Dnmt3b	UTSW	2	153,516,306 (GRCm39)	missense	probably damaging	1.00
R8771:Dnmt3b	UTSW	2	153,504,734 (GRCm39)	missense	possibly damaging	0.94
R8775:Dnmt3b	UTSW	2	153,511,711 (GRCm39)	missense	possibly damaging	0.83
R8775-TAIL:Dnmt3b	UTSW	2	153,511,711 (GRCm39)	missense	possibly damaging	0.83
R8821:Dnmt3b	UTSW	2	153,518,734 (GRCm39)	missense	probably benign	0.15
R8850:Dnmt3b	UTSW	2	153,515,933 (GRCm39)	missense	probably benign	0.16
R9102:Dnmt3b	UTSW	2	153,518,703 (GRCm39)	missense	probably damaging	0.98
R9228:Dnmt3b	UTSW	2	153,507,980 (GRCm39)	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- ATGGTGCTCTTATAAACAGGCG -3'
(R):5'- ACGTTAACCACTGCAGAGTC -3'

Sequencing Primer
(F):5'- GTGCTCTTATAAACAGGCGAGACAC -3'
(R):5'- TGCAGAGTCCAGAGGCATCTATTC -3'

Posted On

2014-06-23