Mutagenetix > Incidental Mutation

Incidental Mutation 'R1753:Dnmt3a'

193773

Institutional Source

Beutler Lab

Gene Symbol

Dnmt3a

Ensembl Gene

ENSMUSG00000020661

Gene Name

DNA methyltransferase 3A

Synonyms

MMRRC Submission

039785-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.460) question?

Stock #

R1753 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

3856007-3964443 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 3923342 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Leucine at position 181 (M181L)

Ref Sequence

ENSEMBL: ENSMUSP00000133501 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020991] [ENSMUST00000172509] [ENSMUST00000172719] [ENSMUST00000174483] [ENSMUST00000174817]

AlphaFold

O88508

Predicted Effect

probably benign
Transcript: ENSMUST00000020991
AA Change: M181L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000020991
Gene: ENSMUSG00000020661
AA Change: M181L

Domain	Start	End	E-Value	Type
low complexity region	2	13	N/A	INTRINSIC
low complexity region	15	37	N/A	INTRINSIC
internal_repeat_1	55	101	6.44e-5	PROSPERO
low complexity region	109	124	N/A	INTRINSIC
low complexity region	160	177	N/A	INTRINSIC
low complexity region	204	215	N/A	INTRINSIC
internal_repeat_1	241	283	6.44e-5	PROSPERO
PWWP	286	344	1.36e-24	SMART
low complexity region	412	430	N/A	INTRINSIC
low complexity region	438	453	N/A	INTRINSIC
PDB:3A1B\|A	454	610	2e-99	PDB
Blast:RING	533	582	1e-17	BLAST
Pfam:DNA_methylase	630	772	2.1e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000172509
AA Change: M107L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000133869
Gene: ENSMUSG00000020661
AA Change: M107L

Domain	Start	End	E-Value	Type
low complexity region	35	50	N/A	INTRINSIC
low complexity region	86	103	N/A	INTRINSIC
low complexity region	130	141	N/A	INTRINSIC
PWWP	212	270	1.36e-24	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000172719
AA Change: M181L

PolyPhen 2 Score 0.541 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000133501
Gene: ENSMUSG00000020661
AA Change: M181L

Domain	Start	End	E-Value	Type
low complexity region	2	13	N/A	INTRINSIC
low complexity region	15	37	N/A	INTRINSIC
low complexity region	109	124	N/A	INTRINSIC
low complexity region	160	177	N/A	INTRINSIC

Predicted Effect

unknown
Transcript: ENSMUST00000173197
AA Change: M56L

SMART Domains

Protein: ENSMUSP00000133567
Gene: ENSMUSG00000020661
AA Change: M56L

Domain	Start	End	E-Value	Type
low complexity region	36	53	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174483

SMART Domains

Protein: ENSMUSP00000133938
Gene: ENSMUSG00000020661

Domain	Start	End	E-Value	Type
low complexity region	35	50	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174817
AA Change: M181L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000134009
Gene: ENSMUSG00000020661
AA Change: M181L

Domain	Start	End	E-Value	Type
low complexity region	2	13	N/A	INTRINSIC
low complexity region	15	37	N/A	INTRINSIC
internal_repeat_1	55	101	6.44e-5	PROSPERO
low complexity region	109	124	N/A	INTRINSIC
low complexity region	160	177	N/A	INTRINSIC
low complexity region	204	215	N/A	INTRINSIC
internal_repeat_1	241	283	6.44e-5	PROSPERO
PWWP	286	344	1.36e-24	SMART
low complexity region	412	430	N/A	INTRINSIC
low complexity region	438	453	N/A	INTRINSIC
PDB:3A1B\|A	454	610	2e-99	PDB
Blast:RING	533	582	1e-17	BLAST
Pfam:DNA_methylase	630	772	2.1e-14	PFAM

Coding Region Coverage

1x: 97.5%
3x: 96.9%
10x: 95.3%
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 causes developmental defects in multiple different organ systems. There is a pseudogene for this gene located on chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Nov 2012]
PHENOTYPE: Homozygotes for a targeted null mutation become runted and die around four weeks of age. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 102 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8b	A	T	11: 109,864,542 (GRCm39)	F409I	probably benign	Het
Adamts19	A	C	18: 59,140,444 (GRCm39)	I848L	possibly damaging	Het
Adamts5	T	C	16: 85,696,240 (GRCm39)	S306G	probably damaging	Het
Adamts8	T	G	9: 30,865,910 (GRCm39)	I486S	probably benign	Het
Adgrg5	T	C	8: 95,668,680 (GRCm39)	F499L	possibly damaging	Het
Akr1c21	T	A	13: 4,627,134 (GRCm39)	C145*	probably null	Het
Anp32b	T	G	4: 46,460,241 (GRCm39)		probably null	Het
Arhgap31	A	G	16: 38,421,974 (GRCm39)	V1364A	possibly damaging	Het
C2cd6	T	C	1: 59,133,992 (GRCm39)	R10G	possibly damaging	Het
Cacna2d1	A	G	5: 16,507,352 (GRCm39)	E367G	possibly damaging	Het
Ccdc81	C	T	7: 89,515,769 (GRCm39)	E637K	probably benign	Het
Cd2	A	T	3: 101,194,815 (GRCm39)	M91K	possibly damaging	Het
Cdc16	C	A	8: 13,814,688 (GRCm39)	Y157*	probably null	Het
Celsr3	G	T	9: 108,709,056 (GRCm39)	V1301F	probably damaging	Het
Cep164	C	T	9: 45,704,235 (GRCm39)	G961S	probably damaging	Het
Cep290	T	C	10: 100,349,843 (GRCm39)	V630A	probably benign	Het
Chd5	C	T	4: 152,463,272 (GRCm39)	S1451F	probably damaging	Het
Cldn23	A	C	8: 36,293,140 (GRCm39)	L116R	possibly damaging	Het
Cngb1	A	T	8: 96,024,401 (GRCm39)		probably benign	Het
Cpb1	G	T	3: 20,320,405 (GRCm39)	N151K	possibly damaging	Het
Cpn2	A	G	16: 30,078,918 (GRCm39)	F261S	probably damaging	Het
Crlf3	A	C	11: 79,948,698 (GRCm39)	V249G	probably damaging	Het
Csmd1	A	T	8: 16,207,134 (GRCm39)	Y1298*	probably null	Het
Cstf2t	C	A	19: 31,061,085 (GRCm39)	P207Q	possibly damaging	Het
Cym	A	C	3: 107,120,741 (GRCm39)	L288R	possibly damaging	Het
Cyp2j12	C	T	4: 96,009,669 (GRCm39)		probably null	Het
Dlx6	C	T	6: 6,863,665 (GRCm39)	Q96*	probably null	Het
Dnah7b	T	C	1: 46,361,495 (GRCm39)	F3465S	probably damaging	Het
Duox1	T	A	2: 122,163,910 (GRCm39)	M859K	probably damaging	Het
Eif2b4	A	T	5: 31,350,284 (GRCm39)	S13T	probably benign	Het
Ercc6	T	C	14: 32,298,956 (GRCm39)	V1448A	probably benign	Het
Esp24	A	G	17: 39,350,893 (GRCm39)	E31G	possibly damaging	Het
F2rl2	T	A	13: 95,837,969 (GRCm39)	M338K	probably benign	Het
Fbxl9	A	T	8: 106,039,824 (GRCm39)	V517E	probably damaging	Het
Fgfbp1	A	C	5: 44,137,265 (GRCm39)	L9R	possibly damaging	Het
Gal3st2b	A	T	1: 93,868,338 (GRCm39)	N188Y	probably damaging	Het
Gpr179	G	C	11: 97,237,404 (GRCm39)	C372W	probably damaging	Het
Grn	T	G	11: 102,324,093 (GRCm39)	C61G	probably damaging	Het
Herc1	T	G	9: 66,376,292 (GRCm39)	C3371G	probably damaging	Het
Herc1	T	C	9: 66,409,366 (GRCm39)		probably null	Het
Hmcn1	C	T	1: 150,462,219 (GRCm39)	G5153D	possibly damaging	Het
Ifi35	A	T	11: 101,347,461 (GRCm39)	R31W	probably damaging	Het
Ifit1bl1	T	A	19: 34,571,260 (GRCm39)	H399L	probably benign	Het
Irx3	G	A	8: 92,527,362 (GRCm39)	P114L	probably damaging	Het
Kat6a	T	A	8: 23,425,813 (GRCm39)	D1119E	probably benign	Het
Kmt2d	G	T	15: 98,741,363 (GRCm39)		probably benign	Het
Kng1	A	T	16: 22,897,869 (GRCm39)	H423L	possibly damaging	Het
Lrp2	T	A	2: 69,326,833 (GRCm39)	Q1746L	possibly damaging	Het
Lrrc63	A	T	14: 75,323,784 (GRCm39)		probably null	Het
Mad2l1	T	A	6: 66,516,797 (GRCm39)	V163E	possibly damaging	Het
Map3k19	A	G	1: 127,750,417 (GRCm39)	M978T	probably benign	Het
Mon1a	A	C	9: 107,778,562 (GRCm39)	N262T	probably damaging	Het
Mpo	A	G	11: 87,686,707 (GRCm39)	N85D	probably benign	Het
Mpp4	T	C	1: 59,183,969 (GRCm39)	D244G	probably null	Het
Mstn	A	G	1: 53,105,717 (GRCm39)	Y353C	probably damaging	Het
Mx1	T	A	16: 97,255,358 (GRCm39)	N232Y	probably damaging	Het
Mycs	T	C	X: 5,380,157 (GRCm39)	R308G	probably benign	Het
Myh11	A	T	16: 14,095,734 (GRCm39)	D9E	probably benign	Het
Nfe2l3	A	T	6: 51,410,392 (GRCm39)	Q169L	probably null	Het
Nr5a1	G	T	2: 38,598,431 (GRCm39)	T122N	possibly damaging	Het
Nras	A	G	3: 102,966,295 (GRCm39)	T20A	probably damaging	Het
Obp2b	T	A	2: 25,628,652 (GRCm39)		probably null	Het
Or1l4	A	G	2: 37,091,439 (GRCm39)	Y62C	probably damaging	Het
Or51g2	T	C	7: 102,622,263 (GRCm39)	N312S	probably benign	Het
Or5aq6	T	C	2: 86,923,571 (GRCm39)	T57A	probably damaging	Het
Or5w18	T	A	2: 87,633,106 (GRCm39)	F124L	probably benign	Het
Or9s14	G	A	1: 92,536,122 (GRCm39)	V188M	probably benign	Het
Pcdh17	A	T	14: 84,715,094 (GRCm39)	T920S	probably benign	Het
Pcdh9	T	C	14: 94,124,661 (GRCm39)	D503G	probably benign	Het
Pcdhb12	C	T	18: 37,569,724 (GRCm39)	T290I	probably damaging	Het
Pde6b	C	A	5: 108,536,557 (GRCm39)	C84*	probably null	Het
Pex1	A	T	5: 3,680,044 (GRCm39)	N914I	probably damaging	Het
Pign	A	G	1: 105,517,042 (GRCm39)	V528A	possibly damaging	Het
Pkhd1	T	G	1: 20,604,129 (GRCm39)	D1187A	possibly damaging	Het
Ppip5k1	T	C	2: 121,173,112 (GRCm39)	K489E	probably damaging	Het
Prob1	T	C	18: 35,786,305 (GRCm39)	T650A	possibly damaging	Het
Radil	T	C	5: 142,481,091 (GRCm39)	Y572C	probably damaging	Het
Rapgef2	A	G	3: 78,996,098 (GRCm39)	I555T	possibly damaging	Het
Rgs5	G	A	1: 169,510,386 (GRCm39)		probably null	Het
Rnaset2b	G	A	17: 7,248,506 (GRCm39)		probably null	Het
S1pr1	A	G	3: 115,505,587 (GRCm39)	S336P	probably benign	Het
Slc24a5	A	G	2: 124,925,115 (GRCm39)	E252G	possibly damaging	Het
Slc34a2	A	T	5: 53,218,733 (GRCm39)	I184F	probably benign	Het
Slc35a3	A	G	3: 116,471,597 (GRCm39)	V224A	possibly damaging	Het
Slc39a9	A	G	12: 80,723,976 (GRCm39)	H211R	probably damaging	Het
Slu7	A	G	11: 43,330,095 (GRCm39)	N174S	probably benign	Het
Smarcd3	A	T	5: 24,800,820 (GRCm39)	Y131*	probably null	Het
Syne1	A	G	10: 5,317,621 (GRCm39)	M491T	probably benign	Het
Tars1	G	A	15: 11,394,329 (GRCm39)	Q103*	probably null	Het
Tmem132d	C	A	5: 127,866,919 (GRCm39)	E660D	probably benign	Het
Ttn	T	C	2: 76,575,387 (GRCm39)	T16842A	probably damaging	Het
Ttn	T	C	2: 76,643,316 (GRCm39)	E13201G	probably damaging	Het
Ttn	T	A	2: 76,582,605 (GRCm39)	M22763L	probably benign	Het
Ubp1	A	T	9: 113,785,037 (GRCm39)	I117L	possibly damaging	Het
Usp24	T	A	4: 106,234,756 (GRCm39)	H954Q	probably benign	Het
Vmn1r174	G	A	7: 23,453,622 (GRCm39)	R96H	probably benign	Het
Vmn2r63	G	A	7: 42,577,669 (GRCm39)	Q290*	probably null	Het
Vnn3	T	C	10: 23,741,718 (GRCm39)	I341T	probably benign	Het
Wbp2nl	A	G	15: 82,189,945 (GRCm39)	T46A	probably damaging	Het
Wdr48	G	T	9: 119,753,313 (GRCm39)	E625*	probably null	Het
Wdr6	C	T	9: 108,452,363 (GRCm39)	V507I	probably damaging	Het
Zp2	A	T	7: 119,737,328 (GRCm39)	W287R	probably benign	Het

Other mutations in Dnmt3a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00844:Dnmt3a	APN	12	3,955,622 (GRCm39)	missense	probably damaging	1.00
IGL02255:Dnmt3a	APN	12	3,922,886 (GRCm39)	splice site	probably benign
IGL02815:Dnmt3a	APN	12	3,954,226 (GRCm39)	critical splice donor site	probably null
IGL03372:Dnmt3a	APN	12	3,952,666 (GRCm39)	missense	probably damaging	1.00
Chromos	UTSW	12	3,951,665 (GRCm39)	missense	probably damaging	1.00
Compaction	UTSW	12	3,916,192 (GRCm39)	nonsense	probably null
R0028:Dnmt3a	UTSW	12	3,950,337 (GRCm39)	missense	probably damaging	0.99
R0306:Dnmt3a	UTSW	12	3,916,096 (GRCm39)	missense	possibly damaging	0.69
R0843:Dnmt3a	UTSW	12	3,922,886 (GRCm39)	splice site	probably benign
R1055:Dnmt3a	UTSW	12	3,922,864 (GRCm39)	missense	probably benign	0.05
R1465:Dnmt3a	UTSW	12	3,916,088 (GRCm39)	missense	probably damaging	1.00
R1465:Dnmt3a	UTSW	12	3,916,088 (GRCm39)	missense	probably damaging	1.00
R1585:Dnmt3a	UTSW	12	3,951,660 (GRCm39)	missense	probably damaging	0.99
R1680:Dnmt3a	UTSW	12	3,923,361 (GRCm39)	missense	probably damaging	0.97
R2055:Dnmt3a	UTSW	12	3,922,859 (GRCm39)	missense	probably benign	0.44
R2219:Dnmt3a	UTSW	12	3,899,654 (GRCm39)	utr 5 prime	probably benign
R2267:Dnmt3a	UTSW	12	3,947,551 (GRCm39)	splice site	probably null
R2359:Dnmt3a	UTSW	12	3,951,599 (GRCm39)	missense	probably damaging	1.00
R2384:Dnmt3a	UTSW	12	3,951,591 (GRCm39)	missense	probably damaging	1.00
R2403:Dnmt3a	UTSW	12	3,949,883 (GRCm39)	missense	probably damaging	1.00
R2884:Dnmt3a	UTSW	12	3,946,132 (GRCm39)	missense	probably damaging	1.00
R3027:Dnmt3a	UTSW	12	3,899,626 (GRCm39)	splice site	probably null
R4281:Dnmt3a	UTSW	12	3,951,665 (GRCm39)	missense	probably damaging	1.00
R4282:Dnmt3a	UTSW	12	3,951,665 (GRCm39)	missense	probably damaging	1.00
R4283:Dnmt3a	UTSW	12	3,951,665 (GRCm39)	missense	probably damaging	1.00
R4809:Dnmt3a	UTSW	12	3,950,352 (GRCm39)	missense	probably damaging	1.00
R5154:Dnmt3a	UTSW	12	3,946,008 (GRCm39)	missense	probably damaging	1.00
R5361:Dnmt3a	UTSW	12	3,945,643 (GRCm39)	missense	probably benign	0.13
R5483:Dnmt3a	UTSW	12	3,949,615 (GRCm39)	missense	probably damaging	1.00
R5768:Dnmt3a	UTSW	12	3,935,660 (GRCm39)	splice site	probably null
R5928:Dnmt3a	UTSW	12	3,916,096 (GRCm39)	missense	possibly damaging	0.69
R6432:Dnmt3a	UTSW	12	3,952,399 (GRCm39)	missense	probably damaging	0.99
R6552:Dnmt3a	UTSW	12	3,957,623 (GRCm39)	missense	probably damaging	1.00
R6783:Dnmt3a	UTSW	12	3,947,406 (GRCm39)	missense	probably damaging	0.99
R6850:Dnmt3a	UTSW	12	3,947,600 (GRCm39)	missense	probably benign	0.40
R7106:Dnmt3a	UTSW	12	3,947,591 (GRCm39)	missense	probably damaging	0.99
R7145:Dnmt3a	UTSW	12	3,922,844 (GRCm39)	missense	probably benign	0.01
R7149:Dnmt3a	UTSW	12	3,952,397 (GRCm39)	missense	probably damaging	1.00
R7239:Dnmt3a	UTSW	12	3,922,850 (GRCm39)	missense	probably benign	0.01
R7490:Dnmt3a	UTSW	12	3,954,204 (GRCm39)	missense	probably damaging	1.00
R7588:Dnmt3a	UTSW	12	3,946,080 (GRCm39)	missense	possibly damaging	0.91
R7684:Dnmt3a	UTSW	12	3,947,340 (GRCm39)	missense	probably benign	0.02
R8058:Dnmt3a	UTSW	12	3,952,768 (GRCm39)	missense	possibly damaging	0.92
R8316:Dnmt3a	UTSW	12	3,946,965 (GRCm39)	missense	probably benign	0.00
R8345:Dnmt3a	UTSW	12	3,885,234 (GRCm39)	missense	unknown
R8464:Dnmt3a	UTSW	12	3,949,635 (GRCm39)	missense	probably benign	0.03
R8914:Dnmt3a	UTSW	12	3,916,192 (GRCm39)	nonsense	probably null
R9131:Dnmt3a	UTSW	12	3,916,136 (GRCm39)	missense	probably benign	0.00
R9246:Dnmt3a	UTSW	12	3,949,204 (GRCm39)	missense	probably damaging	1.00
R9476:Dnmt3a	UTSW	12	3,957,707 (GRCm39)	missense	probably damaging	1.00
R9485:Dnmt3a	UTSW	12	3,916,121 (GRCm39)	missense	probably benign	0.01
R9598:Dnmt3a	UTSW	12	3,946,997 (GRCm39)	missense	probably benign	0.25
R9709:Dnmt3a	UTSW	12	3,957,701 (GRCm39)	missense	probably damaging	1.00
Z1176:Dnmt3a	UTSW	12	3,954,201 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATGAGTCCCTGCCAACTCCTAATCC -3'
(R):5'- AAATCCAGTGGAAGTGCCTGTCGC -3'

Sequencing Primer
(F):5'- TAATCCCTCCTCAGAGGGTCAG -3'
(R):5'- CTAGTAGCAGTTCCTGGAAGCAC -3'

Posted On

2014-05-23