Mutagenetix > Incidental Mutations

Incidental Mutation 'R4870:Dnmt3b'

376480

Institutional Source

Beutler Lab

Gene Symbol

Dnmt3b

Ensembl Gene

ENSMUSG00000027478

Gene Name

DNA methyltransferase 3B

Synonyms

MMRRC Submission

042480-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4870 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

153649450-153687730 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 153670364 bp

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Arginine at position 335 (Q335R)

Ref Sequence

ENSEMBL: ENSMUSP00000105393 (fasta)

Gene Model

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

Predicted Effect

probably benign
Transcript: ENSMUST00000056495
AA Change: Q335R

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000051830
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000072997
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000072761
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000081628
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000080334
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000088976
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000086370
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000103150
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000099439
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000103151
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000099440
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000109771
AA Change: Q335R

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000105393
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000109772
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000105394
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000109773
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000105395
Gene: ENSMUSG00000027478
AA Change: Q335R

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 benign
Transcript: ENSMUST00000109774
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000105396
Gene: ENSMUSG00000027478
AA Change: Q335R

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

noncoding transcript
Transcript: ENSMUST00000132132

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000140811

Meta Mutation Damage Score

0.0687

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.1%

Validation Efficiency

100% (77/77)

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931406P16Rik	C	A	7: 34,284,887	V104L	possibly damaging	Het
Abcb11	A	T	2: 69,239,196	I1285N	probably damaging	Het
Abcc8	G	A	7: 46,107,259	R721*	probably null	Het
Alox8	T	C	11: 69,186,568	Y423C	probably damaging	Het
Ankle2	T	A	5: 110,251,478		probably null	Het
Cdc14a	A	G	3: 116,423,460	I9T	probably benign	Het
Ceacam18	T	C	7: 43,641,904	C257R	probably damaging	Het
Cilp	T	C	9: 65,279,698	V1025A	probably damaging	Het
Clcn7	G	T	17: 25,153,565		probably benign	Het
Csnk1d	A	T	11: 120,983,188		probably benign	Het
Cyp11b2	A	G	15: 74,853,146	S285P	probably benign	Het
Dip2b	T	A	15: 100,195,784		probably null	Het
Dmrt1	T	A	19: 25,505,855	M1K	probably null	Het
Dnajc14	T	C	10: 128,817,350	V684A	probably benign	Het
Exoc3l2	T	A	7: 19,495,192	C772S	unknown	Het
F2rl1	A	T	13: 95,513,984	F130Y	probably damaging	Het
Galk2	C	G	2: 125,929,637	S194*	probably null	Het
Gm7102	C	T	19: 61,175,926	G24R	unknown	Het
Gpbp1l1	A	G	4: 116,573,517	T62A	probably benign	Het
H2-Q10	A	T	17: 35,470,460	D53V	probably damaging	Het
H2-T22	T	C	17: 36,039,032	K356R	probably benign	Het
Insrr	G	A	3: 87,811,604	V956M	probably damaging	Het
Ints7	A	G	1: 191,596,331	T239A	probably damaging	Het
Isl1	A	G	13: 116,308,270		probably benign	Het
Kcng2	A	G	18: 80,322,868	C90R	probably benign	Het
Kif3c	C	T	12: 3,401,735	P171S	probably damaging	Het
Knl1	A	G	2: 119,081,513	T1704A	probably benign	Het
Lats1	A	G	10: 7,705,785	Y778C	probably damaging	Het
Limd2	T	C	11: 106,159,389	M1V	probably null	Het
Mcm10	A	T	2: 5,004,159	I333N	probably damaging	Het
Mipep	T	A	14: 60,802,880	L283*	probably null	Het
Mixl1	A	G	1: 180,694,672	S215P	probably benign	Het
Mmp21	A	G	7: 133,678,677	L188P	probably damaging	Het
Mob1a	T	C	6: 83,340,239	S213P	probably benign	Het
Ndufaf6	T	C	4: 11,060,917	T220A	probably benign	Het
Nr4a3	A	T	4: 48,051,651	Y135F	possibly damaging	Het
Ntn1	CCTTCTTCT	CCTTCT	11: 68,213,026		probably benign	Het
Obscn	A	T	11: 59,136,206	L57Q	probably damaging	Het
Olfr1161	T	C	2: 88,025,460	L246P	probably damaging	Het
Olfr603	T	A	7: 103,383,633	D123V	probably damaging	Het
Pirb	T	A	7: 3,712,662	M839L	probably benign	Het
Plcl2	A	G	17: 50,607,226	E421G	possibly damaging	Het
Ppp1r12b	T	C	1: 134,949,033	N99S	probably benign	Het
Ptpro	A	G	6: 137,377,132	K169E	probably damaging	Het
Rita1	T	A	5: 120,611,383	K88N	probably damaging	Het
Rptn	A	T	3: 93,396,469	K370*	probably null	Het
Simc1	A	G	13: 54,539,763	D115G	probably null	Het
Stab1	T	A	14: 31,142,043	N136I	probably benign	Het
Syt4	T	A	18: 31,447,356		probably benign	Het
Sytl2	A	T	7: 90,388,898	N522I	probably damaging	Het
Tax1bp1	A	G	6: 52,729,493		probably benign	Het
Tenm2	A	T	11: 36,078,569	D847E	probably damaging	Het
Th	G	T	7: 142,894,097	D321E	probably benign	Het
Tmem44	A	T	16: 30,540,773	L46Q	probably damaging	Het
Trp53bp1	A	G	2: 121,256,641	L178P	probably damaging	Het
Trp63	A	G	16: 25,866,218	*285W	probably null	Het
Tsen34	T	C	7: 3,694,381		probably benign	Het
Tssk4	C	T	14: 55,651,815	T256I	probably benign	Het
Ttc17	A	T	2: 94,366,609	N464K	probably damaging	Het
Ttll2	C	T	17: 7,351,599	V310I	probably benign	Het
Ubn1	A	G	16: 5,077,313	E741G	probably damaging	Het
Urad	T	A	5: 147,315,454	I63F	probably damaging	Het
Vcan	T	C	13: 89,704,739	T701A	probably benign	Het
Vmn2r58	A	G	7: 41,837,215	V752A	possibly damaging	Het
Vmn2r69	C	A	7: 85,411,585	V264L	possibly damaging	Het
Zfp292	A	G	4: 34,808,917	S1376P	probably damaging	Het
Zfp955a	G	A	17: 33,241,725	R478*	probably null	Het
Znfx1	A	C	2: 167,055,269	F578L	probably benign	Het

Other mutations in Dnmt3b

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00793:Dnmt3b	APN	2	153672502	missense	possibly damaging	0.88
IGL00931:Dnmt3b	APN	2	153686250	splice site	probably benign
IGL01073:Dnmt3b	APN	2	153670842	splice site	probably benign
IGL01138:Dnmt3b	APN	2	153661441	missense	probably benign	0.01
IGL01960:Dnmt3b	APN	2	153676711	missense	possibly damaging	0.83
IGL02884:Dnmt3b	APN	2	153674377	missense	probably damaging	1.00
IGL03382:Dnmt3b	APN	2	153686359	missense	probably damaging	1.00
PIT4151001:Dnmt3b	UTSW	2	153684479	critical splice donor site	probably null
R0062:Dnmt3b	UTSW	2	153672272	missense	probably benign	0.01
R0122:Dnmt3b	UTSW	2	153676698	missense	probably damaging	1.00
R0147:Dnmt3b	UTSW	2	153661457	missense	possibly damaging	0.68
R0178:Dnmt3b	UTSW	2	153675018	missense	probably benign	0.41
R0751:Dnmt3b	UTSW	2	153674842	splice site	probably null
R1696:Dnmt3b	UTSW	2	153676710	nonsense	probably null
R1795:Dnmt3b	UTSW	2	153683639	missense	possibly damaging	0.92
R1889:Dnmt3b	UTSW	2	153676759	missense	probably benign
R2898:Dnmt3b	UTSW	2	153667630	missense	possibly damaging	0.85
R4201:Dnmt3b	UTSW	2	153670417	nonsense	probably null
R4630:Dnmt3b	UTSW	2	153670315	nonsense	probably null
R5648:Dnmt3b	UTSW	2	153677198	missense	probably damaging	1.00
R5814:Dnmt3b	UTSW	2	153672497	missense	probably benign	0.00
R6311:Dnmt3b	UTSW	2	153674005	missense	probably damaging	1.00
R6625:Dnmt3b	UTSW	2	153665313	missense	probably benign
R6818:Dnmt3b	UTSW	2	153686284	missense	probably damaging	1.00
R7258:Dnmt3b	UTSW	2	153683599	splice site	probably null
R7473:Dnmt3b	UTSW	2	153684450	missense	probably damaging	1.00
R7570:Dnmt3b	UTSW	2	153676699	missense	probably damaging	1.00
R7627:Dnmt3b	UTSW	2	153677580	missense	probably benign	0.03
R7709:Dnmt3b	UTSW	2	153672220	missense	probably benign	0.10
R8483:Dnmt3b	UTSW	2	153674386	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGTTTAGGGAAATGCAGGCCC -3'
(R):5'- TTTTAACAGCCCTGGGTTCCAC -3'

Sequencing Primer
(F):5'- GAAATGCAGGCCCCCAGC -3'
(R):5'- GGCACAATAGGCCTTGCTTG -3'

Posted On

2016-03-17