Incidental Mutation 'R4870:Dnmt3b'
ID 376480
Institutional Source Beutler Lab
Gene Symbol Dnmt3b
Ensembl Gene ENSMUSG00000027478
Gene Name DNA methyltransferase 3B
Synonyms
MMRRC Submission 042480-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4870 (G1)
Quality Score 225
Status Validated
Chromosome 2
Chromosomal Location 153491370-153529650 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 153512284 bp (GRCm39)
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] [ENSMUST00000109773] [ENSMUST00000109772] [ENSMUST00000109771] [ENSMUST00000109774]
AlphaFold O88509
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 noncoding transcript
Transcript: ENSMUST00000140811
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

DomainStartEndE-ValueType
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: ENSMUST00000109772
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000105394
Gene: ENSMUSG00000027478
AA Change: Q335R

DomainStartEndE-ValueType
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: ENSMUST00000109771
AA Change: Q335R

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)
SMART Domains Protein: ENSMUSP00000105393
Gene: ENSMUSG00000027478
AA Change: Q335R

DomainStartEndE-ValueType
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: ENSMUST00000109774
AA Change: Q335R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000105396
Gene: ENSMUSG00000027478
AA Change: Q335R

DomainStartEndE-ValueType
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
Meta Mutation Damage Score 0.0687 question?
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcb11 A T 2: 69,069,540 (GRCm39) I1285N probably damaging Het
Abcc8 G A 7: 45,756,683 (GRCm39) R721* probably null Het
Alox8 T C 11: 69,077,394 (GRCm39) Y423C probably damaging Het
Ankle2 T A 5: 110,399,344 (GRCm39) probably null Het
Cdc14a A G 3: 116,217,109 (GRCm39) I9T probably benign Het
Ceacam18 T C 7: 43,291,328 (GRCm39) C257R probably damaging Het
Cilp T C 9: 65,186,980 (GRCm39) V1025A probably damaging Het
Clcn7 G T 17: 25,372,539 (GRCm39) probably benign Het
Csnk1d A T 11: 120,874,014 (GRCm39) probably benign Het
Cyp11b2 A G 15: 74,724,995 (GRCm39) S285P probably benign Het
Dip2b T A 15: 100,093,665 (GRCm39) probably null Het
Dmrt1 T A 19: 25,483,219 (GRCm39) M1K probably null Het
Dnajc14 T C 10: 128,653,219 (GRCm39) V684A probably benign Het
Exoc3l2 T A 7: 19,229,117 (GRCm39) C772S unknown Het
F2rl1 A T 13: 95,650,492 (GRCm39) F130Y probably damaging Het
Galk2 C G 2: 125,771,557 (GRCm39) S194* probably null Het
Garre1 C A 7: 33,984,312 (GRCm39) V104L possibly damaging Het
Gpbp1l1 A G 4: 116,430,714 (GRCm39) T62A probably benign Het
H2-Q10 A T 17: 35,781,357 (GRCm39) D53V probably damaging Het
H2-T22 T C 17: 36,349,924 (GRCm39) K356R probably benign Het
Insrr G A 3: 87,718,911 (GRCm39) V956M probably damaging Het
Ints7 A G 1: 191,328,443 (GRCm39) T239A probably damaging Het
Isl1 A G 13: 116,444,806 (GRCm39) probably benign Het
Kcng2 A G 18: 80,366,083 (GRCm39) C90R probably benign Het
Kif3c C T 12: 3,451,735 (GRCm39) P171S probably damaging Het
Knl1 A G 2: 118,911,994 (GRCm39) T1704A probably benign Het
Lats1 A G 10: 7,581,549 (GRCm39) Y778C probably damaging Het
Limd2 T C 11: 106,050,215 (GRCm39) M1V probably null Het
Mcm10 A T 2: 5,008,970 (GRCm39) I333N probably damaging Het
Mipep T A 14: 61,040,329 (GRCm39) L283* probably null Het
Mixl1 A G 1: 180,522,237 (GRCm39) S215P probably benign Het
Mmp21 A G 7: 133,280,406 (GRCm39) L188P probably damaging Het
Mob1a T C 6: 83,317,221 (GRCm39) S213P probably benign Het
Mplkipl1 C T 19: 61,164,364 (GRCm39) G24R unknown Het
Ndufaf6 T C 4: 11,060,917 (GRCm39) T220A probably benign Het
Nr4a3 A T 4: 48,051,651 (GRCm39) Y135F possibly damaging Het
Ntn1 CCTTCTTCT CCTTCT 11: 68,103,852 (GRCm39) probably benign Het
Obscn A T 11: 59,027,032 (GRCm39) L57Q probably damaging Het
Or52e19b T A 7: 103,032,840 (GRCm39) D123V probably damaging Het
Or5d35 T C 2: 87,855,804 (GRCm39) L246P probably damaging Het
Pirb T A 7: 3,715,661 (GRCm39) M839L probably benign Het
Plcl2 A G 17: 50,914,254 (GRCm39) E421G possibly damaging Het
Ppp1r12b T C 1: 134,876,771 (GRCm39) N99S probably benign Het
Ptpro A G 6: 137,354,130 (GRCm39) K169E probably damaging Het
Rita1 T A 5: 120,749,448 (GRCm39) K88N probably damaging Het
Rptn A T 3: 93,303,776 (GRCm39) K370* probably null Het
Simc1 A G 13: 54,687,576 (GRCm39) D115G probably null Het
Stab1 T A 14: 30,864,000 (GRCm39) N136I probably benign Het
Syt4 T A 18: 31,580,409 (GRCm39) probably benign Het
Sytl2 A T 7: 90,038,106 (GRCm39) N522I probably damaging Het
Tax1bp1 A G 6: 52,706,478 (GRCm39) probably benign Het
Tenm2 A T 11: 35,969,396 (GRCm39) D847E probably damaging Het
Th G T 7: 142,447,834 (GRCm39) D321E probably benign Het
Tmem44 A T 16: 30,359,591 (GRCm39) L46Q probably damaging Het
Trp53bp1 A G 2: 121,087,122 (GRCm39) L178P probably damaging Het
Trp63 A G 16: 25,684,968 (GRCm39) *285W probably null Het
Tsen34 T C 7: 3,697,380 (GRCm39) probably benign Het
Tssk4 C T 14: 55,889,272 (GRCm39) T256I probably benign Het
Ttc17 A T 2: 94,196,954 (GRCm39) N464K probably damaging Het
Ttll2 C T 17: 7,618,998 (GRCm39) V310I probably benign Het
Ubn1 A G 16: 4,895,177 (GRCm39) E741G probably damaging Het
Urad T A 5: 147,252,264 (GRCm39) I63F probably damaging Het
Vcan T C 13: 89,852,858 (GRCm39) T701A probably benign Het
Vmn2r58 A G 7: 41,486,639 (GRCm39) V752A possibly damaging Het
Vmn2r69 C A 7: 85,060,793 (GRCm39) V264L possibly damaging Het
Zfp292 A G 4: 34,808,917 (GRCm39) S1376P probably damaging Het
Zfp955a G A 17: 33,460,699 (GRCm39) R478* probably null Het
Znfx1 A C 2: 166,897,189 (GRCm39) F578L probably benign Het
Other mutations in Dnmt3b
AlleleSourceChrCoordTypePredicted EffectPPH 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
R0122:Dnmt3b UTSW 2 153,518,618 (GRCm39) missense probably damaging 1.00
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
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'- TGTTTAGGGAAATGCAGGCCC -3'
(R):5'- TTTTAACAGCCCTGGGTTCCAC -3'

Sequencing Primer
(F):5'- GAAATGCAGGCCCCCAGC -3'
(R):5'- GGCACAATAGGCCTTGCTTG -3'
Posted On 2016-03-17