Mutagenetix > Incidental Mutation

Incidental Mutation 'R9476:Dnmt3a'

715801

Institutional Source

Beutler Lab

Gene Symbol

Dnmt3a

Ensembl Gene

ENSMUSG00000020661

Gene Name

DNA methyltransferase 3A

Synonyms

MMRRC Submission

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.404) question?

Stock #

R9476 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

3856007-3964443 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 3957707 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 896 (H896R)

Ref Sequence

ENSEMBL: ENSMUSP00000020991 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020991] [ENSMUST00000111186] [ENSMUST00000172689] [ENSMUST00000172913] [ENSMUST00000174483] [ENSMUST00000174817]

AlphaFold

O88508

Predicted Effect

probably damaging
Transcript: ENSMUST00000020991
AA Change: H896R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000020991
Gene: ENSMUSG00000020661
AA Change: H896R

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 damaging
Transcript: ENSMUST00000111186
AA Change: H677R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106817
Gene: ENSMUSG00000020661
AA Change: H677R

Domain	Start	End	E-Value	Type
PWWP	67	125	1.36e-24	SMART
low complexity region	193	211	N/A	INTRINSIC
low complexity region	219	234	N/A	INTRINSIC
PDB:3A1B\|A	235	391	1e-101	PDB
Blast:RING	314	363	4e-16	BLAST
Pfam:DNA_methylase	411	554	9.5e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000172689
AA Change: H677R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000133543
Gene: ENSMUSG00000020661
AA Change: H677R

Domain	Start	End	E-Value	Type
PWWP	67	125	1.36e-24	SMART
low complexity region	193	211	N/A	INTRINSIC
low complexity region	219	234	N/A	INTRINSIC
PDB:3A1B\|A	235	391	1e-101	PDB
Blast:RING	314	363	4e-16	BLAST
Pfam:DNA_methylase	411	554	9.5e-15	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000172913
AA Change: H57R

PolyPhen 2 Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000134496
Gene: ENSMUSG00000020661
AA Change: H57R

Domain	Start	End	E-Value	Type
PDB:2QRV\|H	1	69	3e-46	PDB
SCOP:d6mhta_	2	66	6e-11	SMART

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: ENSMUST00000174733

SMART Domains

Protein: ENSMUSP00000134492
Gene: ENSMUSG00000020661

Domain	Start	End	E-Value	Type
Pfam:DNA_methylase	16	104	8.2e-10	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000174817
AA Change: H896R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000134009
Gene: ENSMUSG00000020661
AA Change: H896R

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: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930578G10Rik	T	G	4: 42,760,998 (GRCm39)	W6G	unknown	Het
Aatk	A	T	11: 119,901,094 (GRCm39)	C1101S	probably benign	Het
Abcb4	A	T	5: 8,977,790 (GRCm39)	D456V	probably damaging	Het
Abcc8	T	C	7: 45,819,270 (GRCm39)	E186G	possibly damaging	Het
Adam18	T	C	8: 25,115,807 (GRCm39)	N629S	probably benign	Het
Angpt2	T	G	8: 18,764,143 (GRCm39)	N133T	probably benign	Het
Ankrd13c	T	A	3: 157,697,396 (GRCm39)	S334T	probably benign	Het
Ankrd13d	A	T	19: 4,320,289 (GRCm39)	S151T	unknown	Het
Ap3d1	G	A	10: 80,545,655 (GRCm39)	P1025S	probably benign	Het
Bhlhe41	G	A	6: 145,808,948 (GRCm39)	A288V	possibly damaging	Het
Cacna1b	T	C	2: 24,540,058 (GRCm39)	E1467G	probably damaging	Het
Cacna1h	T	A	17: 25,611,524 (GRCm39)	T425S	probably damaging	Het
Cdk13	A	C	13: 17,902,747 (GRCm39)	C934W	probably damaging	Het
Ces1b	T	A	8: 93,799,890 (GRCm39)	N162I	probably damaging	Het
Clec9a	T	A	6: 129,398,023 (GRCm39)	I187K	possibly damaging	Het
Cpsf3	A	G	12: 21,350,080 (GRCm39)	I266M	probably damaging	Het
Cr2	G	T	1: 194,840,416 (GRCm39)	L509M	probably damaging	Het
Creb3l2	C	A	6: 37,311,446 (GRCm39)	G448W	probably damaging	Het
Csmd1	T	A	8: 15,981,215 (GRCm39)		probably null	Het
Cul9	G	A	17: 46,821,833 (GRCm39)	R1881W	probably damaging	Het
Cyth1	C	T	11: 118,076,206 (GRCm39)		probably null	Het
Dnhd1	A	T	7: 105,352,889 (GRCm39)	N2681Y	possibly damaging	Het
Dnm1	T	C	2: 32,213,739 (GRCm39)	M476V	probably benign	Het
Dock1	T	G	7: 134,592,279 (GRCm39)	I938S	probably benign	Het
Dock6	G	A	9: 21,724,821 (GRCm39)	L1515F	probably damaging	Het
Dusp16	T	C	6: 134,695,226 (GRCm39)	H535R	probably benign	Het
Fancd2os	T	A	6: 113,574,994 (GRCm39)	Y4F	probably damaging	Het
Fat4	A	T	3: 39,037,886 (GRCm39)	Q3846L	probably benign	Het
Fbxw10	A	C	11: 62,743,814 (GRCm39)	H240P	probably benign	Het
Frmd4a	A	G	2: 4,608,324 (GRCm39)	T731A	probably benign	Het
Gm44501	T	A	17: 40,889,820 (GRCm39)	H111Q	possibly damaging	Het
Gsdmc	T	C	15: 63,650,551 (GRCm39)	M277V	probably benign	Het
Hira	A	G	16: 18,772,789 (GRCm39)	D867G	probably damaging	Het
Hmcn1	A	G	1: 150,462,127 (GRCm39)	S5184P	probably benign	Het
Ighv1-26	A	C	12: 114,752,407 (GRCm39)	F7V	probably benign	Het
Igkv4-81	C	T	6: 68,967,796 (GRCm39)	E102K	possibly damaging	Het
Inmt	G	T	6: 55,147,990 (GRCm39)	S213Y	possibly damaging	Het
Ints2	T	A	11: 86,135,335 (GRCm39)	M360L	probably benign	Het
Itih3	A	G	14: 30,631,416 (GRCm39)	S827P	probably benign	Het
Itpr3	G	A	17: 27,337,651 (GRCm39)		probably benign	Het
Kcnk12	C	A	17: 88,054,122 (GRCm39)	R180L	probably benign	Het
Kndc1	G	A	7: 139,510,031 (GRCm39)	S1291N	probably benign	Het
Mettl21a	T	C	1: 64,647,285 (GRCm39)	T91A	probably damaging	Het
Mmrn2	A	G	14: 34,120,407 (GRCm39)	I426V	possibly damaging	Het
Mrpl21	T	G	19: 3,337,704 (GRCm39)	V137G	probably damaging	Het
Nrbp2	T	C	15: 75,961,626 (GRCm39)	N218S	probably damaging	Het
Nrip1	T	C	16: 76,089,820 (GRCm39)	N579S	probably benign	Het
Nsf	T	C	11: 103,763,988 (GRCm39)	N365S	probably damaging	Het
Or6c5	A	G	10: 129,074,656 (GRCm39)	I213V	probably damaging	Het
Or7g28	A	T	9: 19,272,383 (GRCm39)	D89E	probably benign	Het
Osbpl3	C	T	6: 50,313,194 (GRCm39)		probably null	Het
Oscar	T	A	7: 3,614,843 (GRCm39)	H43L	probably benign	Het
Pam	C	T	1: 97,826,065 (GRCm39)		probably null	Het
Parn	A	T	16: 13,358,942 (GRCm39)	M600K	probably benign	Het
Pcdha11	C	A	18: 37,139,532 (GRCm39)	T387N	probably benign	Het
Plce1	G	A	19: 38,766,337 (GRCm39)	E2121K	possibly damaging	Het
Prune2	T	A	19: 17,096,706 (GRCm39)	Y737N	possibly damaging	Het
Ptch1	G	A	13: 63,681,448 (GRCm39)	P613L	probably benign	Het
Ptprt	A	C	2: 161,397,381 (GRCm39)	C1129G	probably damaging	Het
Rara	C	T	11: 98,860,983 (GRCm39)	S157L	probably benign	Het
Rest	T	A	5: 77,416,098 (GRCm39)	M104K	probably damaging	Het
Rfc1	A	G	5: 65,437,142 (GRCm39)	S513P	probably damaging	Het
Rnf40	T	A	7: 127,201,808 (GRCm39)	I1000N	probably damaging	Het
Scube2	C	T	7: 109,430,969 (GRCm39)	G410E	probably damaging	Het
Sh3gl2	A	G	4: 85,304,089 (GRCm39)	E264G	probably benign	Het
Shank1	G	A	7: 43,962,342 (GRCm39)	S71N	unknown	Het
Smc4	T	G	3: 68,914,662 (GRCm39)	S92A	probably damaging	Het
Spata31d1b	A	G	13: 59,863,467 (GRCm39)	D205G	probably benign	Het
Spata31e4	A	G	13: 50,856,149 (GRCm39)	T596A	possibly damaging	Het
Spef2	T	C	15: 9,713,203 (GRCm39)	R390G	probably damaging	Het
Speg	T	C	1: 75,377,768 (GRCm39)	F842S	probably damaging	Het
Stk17b	G	T	1: 53,796,898 (GRCm39)	H290N	probably damaging	Het
Stpg3	A	T	2: 25,103,516 (GRCm39)	V191D	probably benign	Het
Supt6	C	T	11: 78,120,290 (GRCm39)	R350H	probably damaging	Het
Tet3	T	C	6: 83,380,935 (GRCm39)	E411G	possibly damaging	Het
Tet3	T	A	6: 83,381,808 (GRCm39)		probably null	Het
Tns3	A	G	11: 8,395,702 (GRCm39)	I1234T	probably damaging	Het
Trim34b	A	G	7: 103,980,503 (GRCm39)	E197G	probably damaging	Het
Vcan	G	T	13: 89,851,531 (GRCm39)	T1143K	possibly damaging	Het
Vmn2r61	T	A	7: 41,949,593 (GRCm39)	V671E	probably damaging	Het
Wdtc1	A	G	4: 133,049,529 (GRCm39)	V29A	probably damaging	Het
Zfp462	G	A	4: 55,080,735 (GRCm39)	M2450I	probably benign	Het
Zfp869	A	T	8: 70,159,849 (GRCm39)	C241*	probably null	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
R1753:Dnmt3a	UTSW	12	3,923,342 (GRCm39)	missense	possibly damaging	0.54
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
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'- GGGAGTGTGAATCTCAAAGCTG -3'
(R):5'- TTCTCTTCTGGGTGCTGAAC -3'

Sequencing Primer
(F):5'- TACCTATCTTTATACCCACAGAGAGG -3'
(R):5'- GGGTGCTGAACTTTTCTCCGTC -3'

Posted On

2022-06-15