Mutagenetix > Incidental Mutations

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

Is this an essential gene?

Possibly essential (E-score: 0.595) question?

Stock #

R4809 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

3806007-3914443 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 3900352 bp

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] [ENSMUST00000174483] [ENSMUST00000174774] [ENSMUST00000174817]

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

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

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 benign
Transcript: ENSMUST00000174774

SMART Domains

Protein: ENSMUSP00000134529
Gene: ENSMUSG00000020661

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

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

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: 32,662,631	V459A	probably benign	Het
Abca12	C	T	1: 71,278,856	A1840T	probably benign	Het
Abhd6	T	G	14: 8,039,771	M1R	probably null	Het
Abl1	T	C	2: 31,800,242	L572P	probably damaging	Het
Adamts2	C	A	11: 50,803,690	S1101R	probably benign	Het
Adgra2	G	A	8: 27,110,479	W200*	probably null	Het
AI661453	C	A	17: 47,467,187		probably benign	Het
Aldh1l2	A	G	10: 83,506,632	F438S	probably damaging	Het
Ankrd49	G	A	9: 14,781,214	T218I	possibly damaging	Het
Ano7	T	C	1: 93,394,566	F410L	probably benign	Het
Aox4	T	A	1: 58,266,649	F1271I	probably damaging	Het
Aqr	T	C	2: 114,175,214		probably benign	Het
Arhgap42	A	G	9: 9,180,117	S54P	probably damaging	Het
Aunip	C	A	4: 134,511,139	D16E	possibly damaging	Het
Btbd7	A	G	12: 102,793,744		probably null	Het
Cabp4	T	C	19: 4,139,291	H89R	probably benign	Het
Ccni	AAA	AAACTAA	5: 93,187,570		probably benign	Het
Chfr	C	T	5: 110,158,834	H410Y	probably damaging	Het
Churc1	C	A	12: 76,782,897	L111M	probably damaging	Het
Clasp1	C	T	1: 118,461,250	T113I	probably benign	Het
Col12a1	T	A	9: 79,693,567	Q745L	probably benign	Het
Col20a1	T	C	2: 180,998,661	L537P	probably damaging	Het
Creb5	A	T	6: 53,610,426	E47V	probably null	Het
Csnk1d	A	T	11: 120,963,842		probably benign	Het
Cts6	A	T	13: 61,202,181	W29R	probably damaging	Het
Dbt	T	A	3: 116,546,343	I420N	probably damaging	Het
Det1	C	A	7: 78,843,807	D150Y	probably damaging	Het
Dlk2	A	G	17: 46,299,014		probably null	Het
Dock9	A	T	14: 121,546,596	Y1989N	probably benign	Het
Dsg4	A	T	18: 20,466,621	T765S	possibly damaging	Het
Epha5	C	T	5: 84,105,891	D548N	possibly damaging	Het
Fam189a1	G	A	7: 64,776,740	T159I	probably damaging	Het
Fam227b	T	A	2: 126,116,125	Y240F	possibly damaging	Het
Fbxw21	C	T	9: 109,143,390	V395I	probably damaging	Het
Fn1	C	A	1: 71,652,800		probably benign	Het
Fpr-rs3	A	T	17: 20,624,421	S153T	probably benign	Het
Frem2	A	G	3: 53,653,895	F1064L	probably benign	Het
Gas2l3	CACTCGTCATACT	CACT	10: 89,430,958		probably benign	Het
Gjd2	C	T	2: 114,011,541	G152R	probably damaging	Het
Gpr75	T	C	11: 30,892,154	I353T	possibly damaging	Het
Grb7	T	C	11: 98,451,436	V145A	possibly damaging	Het
Igkv4-73	G	A	6: 69,197,823	R40W	unknown	Het
Kif1c	C	T	11: 70,726,357	A839V	probably benign	Het
Krt31	G	A	11: 100,049,922	A125V	possibly damaging	Het
Lamb1	A	G	12: 31,278,526	Y163C	probably damaging	Het
Mars	G	T	10: 127,300,215	T535K	probably damaging	Het
Mdc1	T	C	17: 35,849,101		probably null	Het
Micu1	C	T	10: 59,740,822	H167Y	probably benign	Het
Minos1	C	G	4: 139,130,957	W10S	probably damaging	Het
Mrgprb1	C	T	7: 48,447,991	V58I	possibly damaging	Het
Ncoa7	T	A	10: 30,771,762	E6V	possibly damaging	Het
Nectin3	A	C	16: 46,448,160		probably benign	Het
Olfr1085	T	A	2: 86,657,685	M258L	possibly damaging	Het
Olfr1294	C	T	2: 111,537,611	C226Y	probably benign	Het
Olfr46	A	G	7: 140,611,074	K295E	probably damaging	Het
Olfr598	T	A	7: 103,328,523	Y12*	probably null	Het
Pex16	T	C	2: 92,376,638	S54P	probably damaging	Het
Pik3cg	A	T	12: 32,204,081	S636T	possibly damaging	Het
Plin5	A	G	17: 56,116,855	S27P	probably benign	Het
Ptch1	A	T	13: 63,513,708	D1068E	probably damaging	Het
Ptprq	T	C	10: 107,563,175	T1960A	probably damaging	Het
Rap1gap2	T	C	11: 74,407,974		probably benign	Het
Rcc2	G	A	4: 140,717,042	R348Q	probably damaging	Het
Rhbdd3	C	A	11: 5,105,949	A377D	probably damaging	Het
Rpl7	T	G	1: 16,101,965		probably benign	Het
Scn11a	G	T	9: 119,819,870	D42E	probably benign	Het
Scube3	C	T	17: 28,165,173	R549W	probably damaging	Het
Sil1	A	T	18: 35,325,375	M189K	probably damaging	Het
Slc39a6	G	A	18: 24,585,474	Q225*	probably null	Het
Slc7a15	A	T	12: 8,539,002	C182S	probably benign	Het
Spata21	G	A	4: 141,097,120		probably null	Het
Stim2	T	C	5: 54,110,613	V417A	probably damaging	Het
Szt2	T	C	4: 118,388,985	D993G	probably damaging	Het
Tet3	A	G	6: 83,402,946	S747P	probably benign	Het
Tmem86a	C	G	7: 47,052,930	S34R	possibly damaging	Het
Top2b	T	A	14: 16,383,125	S38T	probably benign	Het
Trim33	A	T	3: 103,329,256	T561S	possibly damaging	Het
Ttc39a	C	T	4: 109,416,021	Q25*	probably null	Het
Urb1	A	G	16: 90,759,842	I1816T	possibly damaging	Het
Usp24	T	C	4: 106,413,676		probably null	Het
Usp36	A	C	11: 118,263,070	L840R	probably damaging	Het
Usp50	C	A	2: 126,777,853		probably benign	Het
Vangl2	A	G	1: 172,009,663	V193A	possibly damaging	Het
Vmn1r62	T	A	7: 5,675,867	H182Q	probably benign	Het
Vmn2r124	A	T	17: 18,073,745	Y698F	probably benign	Het
Wls	C	T	3: 159,897,445	T165I	probably benign	Het
Zfp808	G	T	13: 62,171,292	E112*	probably null	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
R1753:Dnmt3a	UTSW	12	3873342	missense	possibly damaging	0.54
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
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
R7588:Dnmt3a	UTSW	12	3896080	missense	possibly damaging	0.91
R7684:Dnmt3a	UTSW	12	3897340	missense	probably benign	0.02
R8058:Dnmt3a	UTSW	12	3902768	missense	possibly damaging	0.92
R8316:Dnmt3a	UTSW	12	3896965	missense	probably benign	0.00
R8345:Dnmt3a	UTSW	12	3835234	missense	unknown
R8464:Dnmt3a	UTSW	12	3899635	missense	probably benign	0.03
R8914:Dnmt3a	UTSW	12	3866192	nonsense	probably null
Z1176:Dnmt3a	UTSW	12	3904201	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