Mutagenetix > Incidental Mutations

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

Is this an essential gene?

Possibly essential (E-score: 0.578) question?

Stock #

R1753 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

3806007-3914443 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 3873342 bp

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]

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: 109,973,716	F409I	probably benign	Het
Adamts19	A	C	18: 59,007,372	I848L	possibly damaging	Het
Adamts5	T	C	16: 85,899,352	S306G	probably damaging	Het
Adamts8	T	G	9: 30,954,614	I486S	probably benign	Het
Adgrg5	T	C	8: 94,942,052	F499L	possibly damaging	Het
Akr1c21	T	A	13: 4,577,135	C145*	probably null	Het
Anp32b	T	G	4: 46,460,241		probably null	Het
Arhgap31	A	G	16: 38,601,612	V1364A	possibly damaging	Het
C2cd6	T	C	1: 59,094,833	R10G	possibly damaging	Het
Cacna2d1	A	G	5: 16,302,354	E367G	possibly damaging	Het
Ccdc81	C	T	7: 89,866,561	E637K	probably benign	Het
Cd2	A	T	3: 101,287,499	M91K	possibly damaging	Het
Cdc16	C	A	8: 13,764,688	Y157*	probably null	Het
Celsr3	G	T	9: 108,831,857	V1301F	probably damaging	Het
Cep164	C	T	9: 45,792,937	G961S	probably damaging	Het
Cep290	T	C	10: 100,513,981	V630A	probably benign	Het
Chd5	C	T	4: 152,378,815	S1451F	probably damaging	Het
Cldn23	A	C	8: 35,825,986	L116R	possibly damaging	Het
Cngb1	A	T	8: 95,297,773		probably benign	Het
Cpb1	G	T	3: 20,266,241	N151K	possibly damaging	Het
Cpn2	A	G	16: 30,260,100	F261S	probably damaging	Het
Crlf3	A	C	11: 80,057,872	V249G	probably damaging	Het
Csmd1	A	T	8: 16,157,120	Y1298*	probably null	Het
Cstf2t	C	A	19: 31,083,685	P207Q	possibly damaging	Het
Cym	A	C	3: 107,213,425	L288R	possibly damaging	Het
Cyp2j12	C	T	4: 96,121,432		probably null	Het
Dlx6	C	T	6: 6,863,665	Q96*	probably null	Het
Dnah7b	T	C	1: 46,322,335	F3465S	probably damaging	Het
Duox1	T	A	2: 122,333,429	M859K	probably damaging	Het
Eif2b4	A	T	5: 31,192,940	S13T	probably benign	Het
Ercc6	T	C	14: 32,576,999	V1448A	probably benign	Het
Esp24	A	G	17: 39,040,002	E31G	possibly damaging	Het
F2rl2	T	A	13: 95,701,461	M338K	probably benign	Het
Fgfbp1	A	C	5: 43,979,923	L9R	possibly damaging	Het
Gal3st2b	A	T	1: 93,940,616	N188Y	probably damaging	Het
Gpr179	G	C	11: 97,346,578	C372W	probably damaging	Het
Grn	T	G	11: 102,433,267	C61G	probably damaging	Het
Herc1	T	G	9: 66,469,010	C3371G	probably damaging	Het
Herc1	T	C	9: 66,502,084		probably null	Het
Hmcn1	C	T	1: 150,586,468	G5153D	possibly damaging	Het
Ifi35	A	T	11: 101,456,635	R31W	probably damaging	Het
Ifit1bl1	T	A	19: 34,593,860	H399L	probably benign	Het
Irx3	G	A	8: 91,800,734	P114L	probably damaging	Het
Kat6a	T	A	8: 22,935,797	D1119E	probably benign	Het
Kmt2d	G	T	15: 98,843,482		probably benign	Het
Kng1	A	T	16: 23,079,119	H423L	possibly damaging	Het
Lrp2	T	A	2: 69,496,489	Q1746L	possibly damaging	Het
Lrrc29	A	T	8: 105,313,192	V517E	probably damaging	Het
Lrrc63	A	T	14: 75,086,344		probably null	Het
Mad2l1	T	A	6: 66,539,813	V163E	possibly damaging	Het
Map3k19	A	G	1: 127,822,680	M978T	probably benign	Het
Mon1a	A	C	9: 107,901,363	N262T	probably damaging	Het
Mpo	A	G	11: 87,795,881	N85D	probably benign	Het
Mpp4	T	C	1: 59,144,810	D244G	probably null	Het
Mstn	A	G	1: 53,066,558	Y353C	probably damaging	Het
Mx1	T	A	16: 97,454,158	N232Y	probably damaging	Het
Mycs	T	C	X: 5,468,103	R308G	probably benign	Het
Myh11	A	T	16: 14,277,870	D9E	probably benign	Het
Nfe2l3	A	T	6: 51,433,412	Q169L	probably null	Het
Nr5a1	G	T	2: 38,708,419	T122N	possibly damaging	Het
Nras	A	G	3: 103,058,979	T20A	probably damaging	Het
Obp2b	T	A	2: 25,738,640		probably null	Het
Olfr1109	T	C	2: 87,093,227	T57A	probably damaging	Het
Olfr1143	T	A	2: 87,802,762	F124L	probably benign	Het
Olfr1410	G	A	1: 92,608,400	V188M	probably benign	Het
Olfr365	A	G	2: 37,201,427	Y62C	probably damaging	Het
Olfr577	T	C	7: 102,973,056	N312S	probably benign	Het
Pcdh17	A	T	14: 84,477,654	T920S	probably benign	Het
Pcdh9	T	C	14: 93,887,225	D503G	probably benign	Het
Pcdhb12	C	T	18: 37,436,671	T290I	probably damaging	Het
Pde6b	C	A	5: 108,388,691	C84*	probably null	Het
Pex1	A	T	5: 3,630,044	N914I	probably damaging	Het
Pign	A	G	1: 105,589,317	V528A	possibly damaging	Het
Pkhd1	T	G	1: 20,533,905	D1187A	possibly damaging	Het
Ppip5k1	T	C	2: 121,342,631	K489E	probably damaging	Het
Prob1	T	C	18: 35,653,252	T650A	possibly damaging	Het
Radil	T	C	5: 142,495,336	Y572C	probably damaging	Het
Rapgef2	A	G	3: 79,088,791	I555T	possibly damaging	Het
Rgs5	G	A	1: 169,682,817		probably null	Het
Rnaset2b	G	A	17: 6,981,107		probably null	Het
S1pr1	A	G	3: 115,711,938	S336P	probably benign	Het
Slc24a5	A	G	2: 125,083,195	E252G	possibly damaging	Het
Slc34a2	A	T	5: 53,061,391	I184F	probably benign	Het
Slc35a3	A	G	3: 116,677,948	V224A	possibly damaging	Het
Slc39a9	A	G	12: 80,677,202	H211R	probably damaging	Het
Slu7	A	G	11: 43,439,268	N174S	probably benign	Het
Smarcd3	A	T	5: 24,595,822	Y131*	probably null	Het
Syne1	A	G	10: 5,367,621	M491T	probably benign	Het
Tars	G	A	15: 11,394,243	Q103*	probably null	Het
Tmem132d	C	A	5: 127,789,855	E660D	probably benign	Het
Ttn	T	C	2: 76,745,043	T16842A	probably damaging	Het
Ttn	T	A	2: 76,752,261	M22763L	probably benign	Het
Ttn	T	C	2: 76,812,972	E13201G	probably damaging	Het
Ubp1	A	T	9: 113,955,969	I117L	possibly damaging	Het
Usp24	T	A	4: 106,377,559	H954Q	probably benign	Het
Vmn1r174	G	A	7: 23,754,197	R96H	probably benign	Het
Vmn2r63	G	A	7: 42,928,245	Q290*	probably null	Het
Vnn3	T	C	10: 23,865,820	I341T	probably benign	Het
Wbp2nl	A	G	15: 82,305,744	T46A	probably damaging	Het
Wdr48	G	T	9: 119,924,247	E625*	probably null	Het
Wdr6	C	T	9: 108,575,164	V507I	probably damaging	Het
Zp2	A	T	7: 120,138,105	W287R	probably benign	Het

Other mutations in Dnmt3a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00844:Dnmt3a	APN	12	3905622	missense	probably damaging	1.00
IGL02255:Dnmt3a	APN	12	3872886	splice site	probably benign
IGL02815:Dnmt3a	APN	12	3904226	critical splice donor site	probably null
IGL03372:Dnmt3a	APN	12	3902666	missense	probably damaging	1.00
R0028:Dnmt3a	UTSW	12	3900337	missense	probably damaging	0.99
R0306:Dnmt3a	UTSW	12	3866096	missense	possibly damaging	0.69
R0843:Dnmt3a	UTSW	12	3872886	splice site	probably benign
R1055:Dnmt3a	UTSW	12	3872864	missense	probably benign	0.05
R1465:Dnmt3a	UTSW	12	3866088	missense	probably damaging	1.00
R1465:Dnmt3a	UTSW	12	3866088	missense	probably damaging	1.00
R1585:Dnmt3a	UTSW	12	3901660	missense	probably damaging	0.99
R1680:Dnmt3a	UTSW	12	3873361	missense	probably damaging	0.97
R2055:Dnmt3a	UTSW	12	3872859	missense	probably benign	0.44
R2219:Dnmt3a	UTSW	12	3849654	utr 5 prime	probably benign
R2267:Dnmt3a	UTSW	12	3897551	splice site	probably null
R2359:Dnmt3a	UTSW	12	3901599	missense	probably damaging	1.00
R2384:Dnmt3a	UTSW	12	3901591	missense	probably damaging	1.00
R2403:Dnmt3a	UTSW	12	3899883	missense	probably damaging	1.00
R2884:Dnmt3a	UTSW	12	3896132	missense	probably damaging	1.00
R3027:Dnmt3a	UTSW	12	3849626	splice site	probably null
R4281:Dnmt3a	UTSW	12	3901665	missense	probably damaging	1.00
R4282:Dnmt3a	UTSW	12	3901665	missense	probably damaging	1.00
R4283:Dnmt3a	UTSW	12	3901665	missense	probably damaging	1.00
R4809:Dnmt3a	UTSW	12	3900352	missense	probably damaging	1.00
R5154:Dnmt3a	UTSW	12	3896008	missense	probably damaging	1.00
R5361:Dnmt3a	UTSW	12	3895643	missense	probably benign	0.13
R5483:Dnmt3a	UTSW	12	3899615	missense	probably damaging	1.00
R5768:Dnmt3a	UTSW	12	3885660	splice site	probably null
R5928:Dnmt3a	UTSW	12	3866096	missense	possibly damaging	0.69
R6432:Dnmt3a	UTSW	12	3902399	missense	probably damaging	0.99
R6552:Dnmt3a	UTSW	12	3907623	missense	probably damaging	1.00
R6783:Dnmt3a	UTSW	12	3897406	missense	probably damaging	0.99
R6850:Dnmt3a	UTSW	12	3897600	missense	probably benign	0.40
R7106:Dnmt3a	UTSW	12	3897591	missense	probably damaging	0.99
R7145:Dnmt3a	UTSW	12	3872844	missense	probably benign	0.01
R7149:Dnmt3a	UTSW	12	3902397	missense	probably damaging	1.00
R7239:Dnmt3a	UTSW	12	3872850	missense	probably benign	0.01
R7490:Dnmt3a	UTSW	12	3904204	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