Mutagenetix > Incidental Mutations

Incidental Mutation 'R2359:Dnmt3a'

247082

Institutional Source

Beutler Lab

Gene Symbol

Dnmt3a

Ensembl Gene

ENSMUSG00000020661

Gene Name

DNA methyltransferase 3A

Synonyms

MMRRC Submission

040341-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.504) question?

Stock #

R2359 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

3806007-3914443 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 3901599 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 659 (S659P)

Ref Sequence

ENSEMBL: ENSMUSP00000134009 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000020991
AA Change: S659P

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

SMART Domains

Protein: ENSMUSP00000020991
Gene: ENSMUSG00000020661
AA Change: S659P

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: S440P

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

SMART Domains

Protein: ENSMUSP00000106817
Gene: ENSMUSG00000020661
AA Change: S440P

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: S440P

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

SMART Domains

Protein: ENSMUSP00000133543
Gene: ENSMUSG00000020661
AA Change: S440P

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

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: S44P

SMART Domains

Protein: ENSMUSP00000134492
Gene: ENSMUSG00000020661
AA Change: S44P

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: S659P

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

SMART Domains

Protein: ENSMUSP00000134009
Gene: ENSMUSG00000020661
AA Change: S659P

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

0.8872

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.4%
20x: 95.3%

Validation Efficiency

95% (41/43)

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: 43 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aaed1	A	T	13: 64,312,651	C12S	probably benign	Het
Adam24	A	G	8: 40,680,945	E484G	possibly damaging	Het
Akr1c20	C	T	13: 4,523,277	G13D	probably damaging	Het
Alkbh3	T	C	2: 94,008,113	T38A	probably benign	Het
Anxa9	A	C	3: 95,302,751	L99R	probably damaging	Het
Arfgef2	A	T	2: 166,860,619	Y826F	probably damaging	Het
Arid2	G	T	15: 96,361,878	L306F	probably damaging	Het
Ccdc141	C	T	2: 77,170,402	V29M	probably damaging	Het
Cd55b	A	G	1: 130,418,121	S187P	probably damaging	Het
Cep63	A	C	9: 102,594,564	L526V	possibly damaging	Het
Chtf8	G	T	8: 106,885,416		probably null	Het
Clca4b	T	A	3: 144,925,242	S286C	probably damaging	Het
Cpsf1	A	G	15: 76,597,673	V1080A	probably benign	Het
Csf2rb2	C	T	15: 78,292,776	V165I	probably benign	Het
Cyp2c40	A	T	19: 39,777,954	V399E	probably damaging	Het
Efr3b	G	A	12: 3,980,136		probably benign	Het
Epha8	A	G	4: 136,946,032	I147T	probably damaging	Het
Fbxo48	G	A	11: 16,953,602	W76*	probably null	Het
Ggt6	A	T	11: 72,437,551	L254F	possibly damaging	Het
Gm11639	T	C	11: 104,739,280	S967P	possibly damaging	Het
Gm4204	T	A	1: 135,232,189		noncoding transcript	Het
Golph3l	A	G	3: 95,591,964		probably null	Het
Gtf2h3	A	G	5: 124,590,876	K166R	probably damaging	Het
Hsp90aa1	A	G	12: 110,694,569		probably null	Het
Hyi	A	G	4: 118,360,341	R79G	probably benign	Het
Igbp1b	G	A	6: 138,657,715	P244S	probably damaging	Het
Ipo8	G	A	6: 148,816,477		probably benign	Het
Larp4b	C	A	13: 9,158,163	T391K	probably damaging	Het
Lrba	T	C	3: 86,348,750	V1133A	probably benign	Het
Med13	C	T	11: 86,291,035		probably benign	Het
Ncapd2	A	G	6: 125,179,416		probably benign	Het
Neurl1b	T	C	17: 26,441,595	F299L	probably benign	Het
Nosip	G	A	7: 45,074,026	A39T	possibly damaging	Het
Nsd1	A	G	13: 55,213,711	D164G	possibly damaging	Het
Ntn1	G	A	11: 68,385,612	T170M	probably damaging	Het
Polrmt	A	T	10: 79,736,562	L1079Q	probably damaging	Het
Rab30	A	G	7: 92,835,797	D129G	possibly damaging	Het
Rwdd2b	C	T	16: 87,436,921	S97N	probably benign	Het
Slitrk3	T	G	3: 73,049,345	D698A	possibly damaging	Het
Smarcd2	T	C	11: 106,267,164	M93V	probably benign	Het
Tmprss4	A	G	9: 45,185,832	V45A	probably benign	Het
Vmn1r22	A	T	6: 57,900,989	M1K	probably null	Het
Vps13a	A	G	19: 16,652,679		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
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
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
R7588:Dnmt3a	UTSW	12	3896080	missense	possibly damaging	0.91
R7684:Dnmt3a	UTSW	12	3897340	missense	probably benign	0.02

Predicted Primers

PCR Primer
(F):5'- TCTGTCCTGGCTTTGGAAAG -3'
(R):5'- AGGAGTGGATGGCAATGTCC -3'

Sequencing Primer
(F):5'- TGAGGCACAGTCATAGCGC -3'
(R):5'- ATGGCAATGTCCCCAGGAG -3'

Posted On

2014-10-30