Mutagenetix > Incidental Mutation

Incidental Mutation 'R0122:Dnmt3b'

21077

Institutional Source

Beutler Lab

Gene Symbol

Dnmt3b

Ensembl Gene

ENSMUSG00000027478

Gene Name

DNA methyltransferase 3B

Synonyms

MMRRC Submission

038407-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0122 (G1)

Quality Score

225

Status

Validated (trace)

Chromosome

Chromosomal Location

153491370-153529650 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 153518618 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 594 (Y594H)

Ref Sequence

ENSEMBL: ENSMUSP00000105396 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056495] [ENSMUST00000072997] [ENSMUST00000081628] [ENSMUST00000088976] [ENSMUST00000103150] [ENSMUST00000103151] [ENSMUST00000109771] [ENSMUST00000109772] [ENSMUST00000109774] [ENSMUST00000109773]

AlphaFold

O88509

Predicted Effect

probably damaging
Transcript: ENSMUST00000056495
AA Change: Y595H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000051830
Gene: ENSMUSG00000027478
AA Change: Y595H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	582	732	3.1e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000072997
AA Change: Y594H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000072761
Gene: ENSMUSG00000027478
AA Change: Y594H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	581	731	4.5e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000081628
AA Change: Y574H

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000080334
Gene: ENSMUSG00000027478
AA Change: Y574H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	1e-54	PDB
Blast:RING	463	512	7e-28	BLAST
Pfam:DNA_methylase	561	711	4.4e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000088976
AA Change: Y594H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000086370
Gene: ENSMUSG00000027478
AA Change: Y594H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	7e-55	PDB
Blast:RING	483	532	5e-28	BLAST
Pfam:DNA_methylase	581	727	2.9e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000103150
AA Change: Y574H

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000099439
Gene: ENSMUSG00000027478
AA Change: Y574H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	8e-55	PDB
Blast:RING	463	512	6e-28	BLAST
Pfam:DNA_methylase	561	707	4.2e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000103151
AA Change: Y574H

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000099440
Gene: ENSMUSG00000027478
AA Change: Y574H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	8e-55	PDB
Blast:RING	463	512	6e-28	BLAST
Pfam:DNA_methylase	561	707	4.2e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000109771
AA Change: Y595H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000105393
Gene: ENSMUSG00000027478
AA Change: Y595H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	582	732	3.1e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000109772
AA Change: Y594H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000105394
Gene: ENSMUSG00000027478
AA Change: Y594H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	7e-55	PDB
Blast:RING	483	532	5e-28	BLAST
Pfam:DNA_methylase	581	727	2.9e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000109774
AA Change: Y594H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000105396
Gene: ENSMUSG00000027478
AA Change: Y594H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
low complexity region	380	389	N/A	INTRINSIC
PDB:3A1A\|A	421	560	8e-55	PDB
Blast:RING	483	532	6e-28	BLAST
Pfam:DNA_methylase	581	731	4.5e-15	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000109773
AA Change: Y574H

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000105395
Gene: ENSMUSG00000027478
AA Change: Y574H

Domain	Start	End	E-Value	Type
low complexity region	57	74	N/A	INTRINSIC
low complexity region	79	97	N/A	INTRINSIC
low complexity region	157	179	N/A	INTRINSIC
PWWP	230	288	2.43e-26	SMART
PDB:3A1A\|A	401	540	1e-54	PDB
Blast:RING	463	512	7e-28	BLAST
Pfam:DNA_methylase	561	711	4.4e-15	PFAM

Meta Mutation Damage Score

0.5644

Coding Region Coverage

1x: 99.1%
3x: 98.2%
10x: 95.9%
20x: 91.3%

Validation Efficiency

99% (78/79)

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 results in severe developmental defects and loss of viability. Mutation of the related gene in humans causes immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. There is a pseudogene for this gene located adjacent to this gene in the same region of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Nov 2012]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit growth retardation and rostral neural tube defects, and die prenatally. Mutants exhibit slight under-methylation of endogenous viral DNA and substantial demethylation of minor satellite DNA. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2010315B03Rik	T	C	9: 124,057,789 (GRCm39)		probably benign	Het
Adam12	T	A	7: 133,614,077 (GRCm39)	I60F	probably benign	Het
Adamts10	A	G	17: 33,747,454 (GRCm39)		probably benign	Het
Adamts12	C	T	15: 11,215,710 (GRCm39)	R244C	probably damaging	Het
Adamts7	A	G	9: 90,061,474 (GRCm39)	E360G	probably damaging	Het
Atn1	A	T	6: 124,720,197 (GRCm39)		probably benign	Het
Avl9	G	T	6: 56,713,468 (GRCm39)	R242L	probably benign	Het
Baz2b	G	T	2: 59,743,963 (GRCm39)		probably null	Het
Bloc1s6	G	C	2: 122,587,963 (GRCm39)		probably benign	Het
Btbd9	C	T	17: 30,493,916 (GRCm39)	D492N	possibly damaging	Het
C1qa	T	A	4: 136,625,142 (GRCm39)	T3S	probably benign	Het
Cacna1e	A	T	1: 154,319,647 (GRCm39)	F1351Y	probably damaging	Het
Car9	C	T	4: 43,512,206 (GRCm39)	A356V	probably benign	Het
Ccdc116	T	A	16: 16,960,598 (GRCm39)	D73V	probably damaging	Het
Ces2g	T	C	8: 105,694,932 (GRCm39)	Y518H	probably damaging	Het
Ciz1	A	G	2: 32,261,431 (GRCm39)		probably benign	Het
Cmc1	A	T	9: 117,894,388 (GRCm39)	C29S	probably damaging	Het
Coil	T	A	11: 88,875,833 (GRCm39)		probably benign	Het
Col3a1	C	T	1: 45,380,057 (GRCm39)		probably benign	Het
Cox15	A	G	19: 43,737,229 (GRCm39)	I135T	possibly damaging	Het
Cyld	T	C	8: 89,468,920 (GRCm39)	S564P	probably damaging	Het
Dnah5	T	A	15: 28,378,509 (GRCm39)	N2948K	probably damaging	Het
Dnah7a	G	A	1: 53,436,301 (GRCm39)	R4014W	probably damaging	Het
Dntt	A	G	19: 41,041,477 (GRCm39)	K387R	possibly damaging	Het
Efcab7	G	A	4: 99,749,560 (GRCm39)		probably benign	Het
Flvcr1	G	T	1: 190,753,423 (GRCm39)	P250T	possibly damaging	Het
Gga2	C	A	7: 121,590,797 (GRCm39)	V504L	probably damaging	Het
Gm12239	T	A	11: 55,906,738 (GRCm39)		noncoding transcript	Het
Gm6327	T	C	16: 12,578,890 (GRCm39)		noncoding transcript	Het
Krt26	G	T	11: 99,224,545 (GRCm39)	Y324*	probably null	Het
Lamb2	A	T	9: 108,363,713 (GRCm39)	H939L	probably benign	Het
Lipo3	C	T	19: 33,600,086 (GRCm39)		probably benign	Het
Mmp1b	G	A	9: 7,386,689 (GRCm39)	T145M	probably damaging	Het
Mrps27	G	T	13: 99,501,736 (GRCm39)	V76L	probably benign	Het
Mup6	T	A	4: 60,003,995 (GRCm39)	Y29*	probably null	Het
Nlrc3	T	C	16: 3,776,822 (GRCm39)	K756E	probably damaging	Het
Nnt	T	C	13: 119,505,133 (GRCm39)	H527R	probably damaging	Het
Nudt8	T	C	19: 4,051,306 (GRCm39)	V59A	probably benign	Het
Ofcc1	A	T	13: 40,434,032 (GRCm39)		probably null	Het
Or10d1	A	T	9: 39,484,020 (GRCm39)	D178E	probably damaging	Het
Or2a25	T	C	6: 42,888,889 (GRCm39)	V144A	probably benign	Het
Or51q1c	T	C	7: 103,652,565 (GRCm39)	W28R	probably damaging	Het
Pdgfd	T	C	9: 6,293,851 (GRCm39)	S142P	probably damaging	Het
Pias4	G	T	10: 80,992,921 (GRCm39)	Q22K	probably damaging	Het
Pin1	T	C	9: 20,573,600 (GRCm39)	I95T	probably benign	Het
Pramel23	A	T	4: 143,424,974 (GRCm39)	D156E	probably benign	Het
Prickle2	G	A	6: 92,388,326 (GRCm39)	Q359*	probably null	Het
Qrich2	G	T	11: 116,337,639 (GRCm39)	Q1950K	possibly damaging	Het
Rab10	C	A	12: 3,359,357 (GRCm39)	G21V	probably damaging	Het
Rbm27	T	A	18: 42,447,033 (GRCm39)		probably benign	Het
Samd4	C	A	14: 47,254,017 (GRCm39)	S160R	probably benign	Het
Scube3	A	C	17: 28,385,502 (GRCm39)		probably benign	Het
Serpinf2	A	G	11: 75,327,372 (GRCm39)	L185P	probably damaging	Het
Slc16a12	A	G	19: 34,652,264 (GRCm39)	I294T	probably benign	Het
Slc45a3	T	A	1: 131,905,478 (GRCm39)	M167K	probably damaging	Het
Sspo	T	A	6: 48,450,910 (GRCm39)	L2673Q	possibly damaging	Het
Supt3	A	G	17: 45,314,028 (GRCm39)	D139G	probably damaging	Het
Tas1r3	T	C	4: 155,945,290 (GRCm39)	M644V	probably benign	Het
Tgfbi	A	G	13: 56,775,781 (GRCm39)	T276A	probably damaging	Het
Tmem177	T	C	1: 119,838,308 (GRCm39)	I124V	probably benign	Het
Tmprss11f	G	T	5: 86,681,484 (GRCm39)		probably benign	Het
Tmprss3	G	A	17: 31,412,876 (GRCm39)		probably benign	Het
Twf1	A	G	15: 94,484,430 (GRCm39)		probably benign	Het
Uba52	T	A	8: 70,961,951 (GRCm39)	Q166L	probably damaging	Het
Ubr3	G	T	2: 69,809,756 (GRCm39)	G1242V	probably damaging	Het
Unc13d	C	T	11: 115,956,308 (GRCm39)	S835N	probably benign	Het
Ush2a	A	G	1: 188,680,652 (GRCm39)	K4877E	possibly damaging	Het
Vmn2r98	A	G	17: 19,286,662 (GRCm39)	I387V	probably benign	Het
Vps11	A	T	9: 44,265,809 (GRCm39)	I490N	probably damaging	Het
Vstm4	T	A	14: 32,585,768 (GRCm39)		probably null	Het
Zfp110	C	A	7: 12,582,524 (GRCm39)	H391N	possibly damaging	Het
Zfp212	C	T	6: 47,907,957 (GRCm39)	P312L	possibly damaging	Het
Zfp329	A	T	7: 12,544,914 (GRCm39)	H203Q	probably damaging	Het
Zscan12	G	A	13: 21,553,139 (GRCm39)	G321E	probably damaging	Het

Other mutations in Dnmt3b

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00793:Dnmt3b	APN	2	153,514,422 (GRCm39)	missense	possibly damaging	0.88
IGL00931:Dnmt3b	APN	2	153,528,170 (GRCm39)	splice site	probably benign
IGL01073:Dnmt3b	APN	2	153,512,762 (GRCm39)	splice site	probably benign
IGL01138:Dnmt3b	APN	2	153,503,361 (GRCm39)	missense	probably benign	0.01
IGL01960:Dnmt3b	APN	2	153,518,631 (GRCm39)	missense	possibly damaging	0.83
IGL02884:Dnmt3b	APN	2	153,516,297 (GRCm39)	missense	probably damaging	1.00
IGL03382:Dnmt3b	APN	2	153,528,279 (GRCm39)	missense	probably damaging	1.00
PIT4151001:Dnmt3b	UTSW	2	153,526,399 (GRCm39)	critical splice donor site	probably null
R0062:Dnmt3b	UTSW	2	153,514,192 (GRCm39)	missense	probably benign	0.01
R0147:Dnmt3b	UTSW	2	153,503,377 (GRCm39)	missense	possibly damaging	0.68
R0178:Dnmt3b	UTSW	2	153,516,938 (GRCm39)	missense	probably benign	0.41
R0751:Dnmt3b	UTSW	2	153,516,762 (GRCm39)	splice site	probably null
R1696:Dnmt3b	UTSW	2	153,518,630 (GRCm39)	nonsense	probably null
R1795:Dnmt3b	UTSW	2	153,525,559 (GRCm39)	missense	possibly damaging	0.92
R1889:Dnmt3b	UTSW	2	153,518,679 (GRCm39)	missense	probably benign
R2898:Dnmt3b	UTSW	2	153,509,550 (GRCm39)	missense	possibly damaging	0.85
R4201:Dnmt3b	UTSW	2	153,512,337 (GRCm39)	nonsense	probably null
R4630:Dnmt3b	UTSW	2	153,512,235 (GRCm39)	nonsense	probably null
R4870:Dnmt3b	UTSW	2	153,512,284 (GRCm39)	missense	probably benign	0.01
R5648:Dnmt3b	UTSW	2	153,519,118 (GRCm39)	missense	probably damaging	1.00
R5814:Dnmt3b	UTSW	2	153,514,417 (GRCm39)	missense	probably benign	0.00
R6311:Dnmt3b	UTSW	2	153,515,925 (GRCm39)	missense	probably damaging	1.00
R6625:Dnmt3b	UTSW	2	153,507,233 (GRCm39)	missense	probably benign
R6818:Dnmt3b	UTSW	2	153,528,204 (GRCm39)	missense	probably damaging	1.00
R7258:Dnmt3b	UTSW	2	153,525,519 (GRCm39)	splice site	probably null
R7473:Dnmt3b	UTSW	2	153,526,370 (GRCm39)	missense	probably damaging	1.00
R7570:Dnmt3b	UTSW	2	153,518,619 (GRCm39)	missense	probably damaging	1.00
R7627:Dnmt3b	UTSW	2	153,519,500 (GRCm39)	missense	probably benign	0.03
R7709:Dnmt3b	UTSW	2	153,514,140 (GRCm39)	missense	probably benign	0.10
R8483:Dnmt3b	UTSW	2	153,516,306 (GRCm39)	missense	probably damaging	1.00
R8771:Dnmt3b	UTSW	2	153,504,734 (GRCm39)	missense	possibly damaging	0.94
R8775:Dnmt3b	UTSW	2	153,511,711 (GRCm39)	missense	possibly damaging	0.83
R8775-TAIL:Dnmt3b	UTSW	2	153,511,711 (GRCm39)	missense	possibly damaging	0.83
R8821:Dnmt3b	UTSW	2	153,518,734 (GRCm39)	missense	probably benign	0.15
R8850:Dnmt3b	UTSW	2	153,515,933 (GRCm39)	missense	probably benign	0.16
R9102:Dnmt3b	UTSW	2	153,518,703 (GRCm39)	missense	probably damaging	0.98
R9228:Dnmt3b	UTSW	2	153,507,980 (GRCm39)	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- TTTCCAGCAGGCAGTGCTCTTC -3'
(R):5'- TACAGCTTGTCCCACCTGCAAC -3'

Sequencing Primer
(F):5'- GGAAGGTCATACGTCTTAGCTC -3'
(R):5'- TGGGGACAGCATGAGACC -3'

Posted On

2013-04-11