Mutagenetix > Incidental Mutation

Incidental Mutation 'R4809:Dnmt3a'

370931

Institutional Source

Beutler Lab

Gene Symbol

Dnmt3a

Ensembl Gene

ENSMUSG00000020661

Gene Name

DNA methyltransferase 3A

Synonyms

MMRRC Submission

042428-MU

Accession Numbers

Essential gene?

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

Stock #

R4809 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

3856007-3964443 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 3950352 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 639 (I639F)

Ref Sequence

ENSEMBL: ENSMUSP00000134009 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020991] [ENSMUST00000111186] [ENSMUST00000172509] [ENSMUST00000172689] [ENSMUST00000172879] [ENSMUST00000174102] [ENSMUST00000174817] [ENSMUST00000174483] [ENSMUST00000174774]

AlphaFold

O88508

Predicted Effect

probably damaging
Transcript: ENSMUST00000020991
AA Change: I639F

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

SMART Domains

Protein: ENSMUSP00000020991
Gene: ENSMUSG00000020661
AA Change: I639F

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: I420F

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

SMART Domains

Protein: ENSMUSP00000106817
Gene: ENSMUSG00000020661
AA Change: I420F

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 benign
Transcript: ENSMUST00000172509

SMART Domains

Protein: ENSMUSP00000133869
Gene: ENSMUSG00000020661

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

probably damaging
Transcript: ENSMUST00000172689
AA Change: I420F

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

SMART Domains

Protein: ENSMUSP00000133543
Gene: ENSMUSG00000020661
AA Change: I420F

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 benign
Transcript: ENSMUST00000172749

SMART Domains

Protein: ENSMUSP00000134567
Gene: ENSMUSG00000020661

Domain	Start	End	E-Value	Type
PWWP	61	119	7.62e-19	SMART
low complexity region	151	169	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000172879

Predicted Effect

probably benign
Transcript: ENSMUST00000174102

SMART Domains

Protein: ENSMUSP00000134480
Gene: ENSMUSG00000020661

Domain	Start	End	E-Value	Type
Pfam:PWWP	101	140	2e-10	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000174733
AA Change: I24F

SMART Domains

Protein: ENSMUSP00000134492
Gene: ENSMUSG00000020661
AA Change: I24F

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000174817
AA Change: I639F

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

SMART Domains

Protein: ENSMUSP00000134009
Gene: ENSMUSG00000020661
AA Change: I639F

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

noncoding transcript
Transcript: ENSMUST00000174272

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: ENSMUST00000174774

SMART Domains

Protein: ENSMUSP00000134529
Gene: ENSMUSG00000020661

Domain	Start	End	E-Value	Type
PWWP	67	125	1.36e-24	SMART

Meta Mutation Damage Score

0.8056

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.0%

Validation Efficiency

96% (96/100)

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3425401B19Rik	A	G	14: 32,384,588 (GRCm39)	V459A	probably benign	Het
Abca12	C	T	1: 71,318,015 (GRCm39)	A1840T	probably benign	Het
Abhd6	T	G	14: 8,039,771 (GRCm38)	M1R	probably null	Het
Abl1	T	C	2: 31,690,254 (GRCm39)	L572P	probably damaging	Het
Adamts2	C	A	11: 50,694,517 (GRCm39)	S1101R	probably benign	Het
Adgra2	G	A	8: 27,600,507 (GRCm39)	W200*	probably null	Het
AI661453	C	A	17: 47,778,112 (GRCm39)		probably benign	Het
Aldh1l2	A	G	10: 83,342,496 (GRCm39)	F438S	probably damaging	Het
Ankrd49	G	A	9: 14,692,510 (GRCm39)	T218I	possibly damaging	Het
Ano7	T	C	1: 93,322,288 (GRCm39)	F410L	probably benign	Het
Aox4	T	A	1: 58,305,808 (GRCm39)	F1271I	probably damaging	Het
Aqr	T	C	2: 114,005,695 (GRCm39)		probably benign	Het
Arhgap42	A	G	9: 9,180,118 (GRCm39)	S54P	probably damaging	Het
Aunip	C	A	4: 134,238,450 (GRCm39)	D16E	possibly damaging	Het
Btbd7	A	G	12: 102,760,003 (GRCm39)		probably null	Het
Cabp4	T	C	19: 4,189,290 (GRCm39)	H89R	probably benign	Het
Ccni	AAA	AAACTAA	5: 93,335,429 (GRCm39)		probably benign	Het
Chfr	C	T	5: 110,306,700 (GRCm39)	H410Y	probably damaging	Het
Churc1	C	A	12: 76,829,671 (GRCm39)	L111M	probably damaging	Het
Clasp1	C	T	1: 118,388,980 (GRCm39)	T113I	probably benign	Het
Col12a1	T	A	9: 79,600,849 (GRCm39)	Q745L	probably benign	Het
Col20a1	T	C	2: 180,640,454 (GRCm39)	L537P	probably damaging	Het
Creb5	A	T	6: 53,587,411 (GRCm39)	E47V	probably null	Het
Csnk1d	A	T	11: 120,854,668 (GRCm39)		probably benign	Het
Cts6	A	T	13: 61,349,995 (GRCm39)	W29R	probably damaging	Het
Dbt	T	A	3: 116,339,992 (GRCm39)	I420N	probably damaging	Het
Det1	C	A	7: 78,493,555 (GRCm39)	D150Y	probably damaging	Het
Dlk2	A	G	17: 46,609,940 (GRCm39)		probably null	Het
Dock9	A	T	14: 121,784,008 (GRCm39)	Y1989N	probably benign	Het
Dsg4	A	T	18: 20,599,678 (GRCm39)	T765S	possibly damaging	Het
Entrep2	G	A	7: 64,426,488 (GRCm39)	T159I	probably damaging	Het
Epha5	C	T	5: 84,253,750 (GRCm39)	D548N	possibly damaging	Het
Fam227b	T	A	2: 125,958,045 (GRCm39)	Y240F	possibly damaging	Het
Fbxw21	C	T	9: 108,972,458 (GRCm39)	V395I	probably damaging	Het
Fn1	C	A	1: 71,691,959 (GRCm39)		probably benign	Het
Fpr-rs3	A	T	17: 20,844,683 (GRCm39)	S153T	probably benign	Het
Frem2	A	G	3: 53,561,316 (GRCm39)	F1064L	probably benign	Het
Gas2l3	CACTCGTCATACT	CACT	10: 89,266,820 (GRCm39)		probably benign	Het
Gjd2	C	T	2: 113,842,022 (GRCm39)	G152R	probably damaging	Het
Gpr75	T	C	11: 30,842,154 (GRCm39)	I353T	possibly damaging	Het
Grb7	T	C	11: 98,342,262 (GRCm39)	V145A	possibly damaging	Het
Igkv4-73	G	A	6: 69,174,807 (GRCm39)	R40W	unknown	Het
Kif1c	C	T	11: 70,617,183 (GRCm39)	A839V	probably benign	Het
Krt31	G	A	11: 99,940,748 (GRCm39)	A125V	possibly damaging	Het
Lamb1	A	G	12: 31,328,525 (GRCm39)	Y163C	probably damaging	Het
Mars1	G	T	10: 127,136,084 (GRCm39)	T535K	probably damaging	Het
Mdc1	T	C	17: 36,159,993 (GRCm39)		probably null	Het
Micos10	C	G	4: 138,858,268 (GRCm39)	W10S	probably damaging	Het
Micu1	C	T	10: 59,576,644 (GRCm39)	H167Y	probably benign	Het
Mrgprb1	C	T	7: 48,097,739 (GRCm39)	V58I	possibly damaging	Het
Ncoa7	T	A	10: 30,647,758 (GRCm39)	E6V	possibly damaging	Het
Nectin3	A	C	16: 46,268,523 (GRCm39)		probably benign	Het
Or13a18	A	G	7: 140,190,987 (GRCm39)	K295E	probably damaging	Het
Or4k44	C	T	2: 111,367,956 (GRCm39)	C226Y	probably benign	Het
Or52ab7	T	A	7: 102,977,730 (GRCm39)	Y12*	probably null	Het
Or8k38	T	A	2: 86,488,029 (GRCm39)	M258L	possibly damaging	Het
Pex16	T	C	2: 92,206,983 (GRCm39)	S54P	probably damaging	Het
Pik3cg	A	T	12: 32,254,080 (GRCm39)	S636T	possibly damaging	Het
Plin5	A	G	17: 56,423,855 (GRCm39)	S27P	probably benign	Het
Ptch1	A	T	13: 63,661,522 (GRCm39)	D1068E	probably damaging	Het
Ptprq	T	C	10: 107,399,036 (GRCm39)	T1960A	probably damaging	Het
Rap1gap2	T	C	11: 74,298,800 (GRCm39)		probably benign	Het
Rcc2	G	A	4: 140,444,353 (GRCm39)	R348Q	probably damaging	Het
Rhbdd3	C	A	11: 5,055,949 (GRCm39)	A377D	probably damaging	Het
Rpl7	T	G	1: 16,172,189 (GRCm39)		probably benign	Het
Scn11a	G	T	9: 119,648,936 (GRCm39)	D42E	probably benign	Het
Scube3	C	T	17: 28,384,147 (GRCm39)	R549W	probably damaging	Het
Sil1	A	T	18: 35,458,428 (GRCm39)	M189K	probably damaging	Het
Slc39a6	G	A	18: 24,718,531 (GRCm39)	Q225*	probably null	Het
Slc7a15	A	T	12: 8,589,002 (GRCm39)	C182S	probably benign	Het
Spata21	G	A	4: 140,824,431 (GRCm39)		probably null	Het
Stim2	T	C	5: 54,267,955 (GRCm39)	V417A	probably damaging	Het
Szt2	T	C	4: 118,246,182 (GRCm39)	D993G	probably damaging	Het
Tet3	A	G	6: 83,379,928 (GRCm39)	S747P	probably benign	Het
Tmem86a	C	G	7: 46,702,678 (GRCm39)	S34R	possibly damaging	Het
Top2b	T	A	14: 16,383,125 (GRCm38)	S38T	probably benign	Het
Trim33	A	T	3: 103,236,572 (GRCm39)	T561S	possibly damaging	Het
Ttc39a	C	T	4: 109,273,218 (GRCm39)	Q25*	probably null	Het
Urb1	A	G	16: 90,556,730 (GRCm39)	I1816T	possibly damaging	Het
Usp24	T	C	4: 106,270,873 (GRCm39)		probably null	Het
Usp36	A	C	11: 118,153,896 (GRCm39)	L840R	probably damaging	Het
Usp50	C	A	2: 126,619,773 (GRCm39)		probably benign	Het
Vangl2	A	G	1: 171,837,230 (GRCm39)	V193A	possibly damaging	Het
Vmn1r62	T	A	7: 5,678,866 (GRCm39)	H182Q	probably benign	Het
Vmn2r124	A	T	17: 18,294,007 (GRCm39)	Y698F	probably benign	Het
Wls	C	T	3: 159,603,082 (GRCm39)	T165I	probably benign	Het
Zfp808	G	T	13: 62,319,106 (GRCm39)	E112*	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
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'- AAGCCCTGTAGTTCTCAGCG -3'
(R):5'- ACTAGAATATGTGTTAGCATGCTTG -3'

Sequencing Primer
(F):5'- CCTGTAGTTCTCAGCGGGAGG -3'
(R):5'- AGGATTGTAGACCATGCTAGCCTC -3'

Posted On

2016-02-04