Incidental Mutation 'R8850:Dnmt3b'
ID 674927
Institutional Source Beutler Lab
Gene Symbol Dnmt3b
Ensembl Gene ENSMUSG00000027478
Gene Name DNA methyltransferase 3B
Synonyms
MMRRC Submission 068673-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R8850 (G1)
Quality Score 225.009
Status Validated
Chromosome 2
Chromosomal Location 153491370-153529650 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 153515933 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Tyrosine at position 447 (N447Y)
Ref Sequence ENSEMBL: ENSMUSP00000072761 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000056495] [ENSMUST00000072997] [ENSMUST00000081628] [ENSMUST00000088976] [ENSMUST00000103150] [ENSMUST00000103151] [ENSMUST00000109771] [ENSMUST00000109772] [ENSMUST00000109773] [ENSMUST00000109774]
AlphaFold O88509
Predicted Effect probably benign
Transcript: ENSMUST00000056495
AA Change: N447Y

PolyPhen 2 Score 0.077 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000051830
Gene: ENSMUSG00000027478
AA Change: N447Y

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: N447Y

PolyPhen 2 Score 0.158 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000072761
Gene: ENSMUSG00000027478
AA Change: N447Y

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 damaging
Transcript: ENSMUST00000081628
AA Change: N427Y

PolyPhen 2 Score 0.962 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000080334
Gene: ENSMUSG00000027478
AA Change: N427Y

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 possibly damaging
Transcript: ENSMUST00000088976
AA Change: N447Y

PolyPhen 2 Score 0.931 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000086370
Gene: ENSMUSG00000027478
AA Change: N447Y

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 possibly damaging
Transcript: ENSMUST00000103150
AA Change: N427Y

PolyPhen 2 Score 0.866 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000099439
Gene: ENSMUSG00000027478
AA Change: N427Y

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 possibly damaging
Transcript: ENSMUST00000103151
AA Change: N427Y

PolyPhen 2 Score 0.866 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000099440
Gene: ENSMUSG00000027478
AA Change: N427Y

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: ENSMUST00000109771
AA Change: N447Y

PolyPhen 2 Score 0.077 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000105393
Gene: ENSMUSG00000027478
AA Change: N447Y

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 possibly damaging
Transcript: ENSMUST00000109772
AA Change: N447Y

PolyPhen 2 Score 0.931 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000105394
Gene: ENSMUSG00000027478
AA Change: N447Y

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 damaging
Transcript: ENSMUST00000109773
AA Change: N427Y

PolyPhen 2 Score 0.962 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000105395
Gene: ENSMUSG00000027478
AA Change: N427Y

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: ENSMUST00000109774
AA Change: N447Y

PolyPhen 2 Score 0.158 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000105396
Gene: ENSMUSG00000027478
AA Change: N447Y

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency 100% (64/64)
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: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Actr10 G A 12: 70,989,032 (GRCm39) probably null Het
Adgrd1 A G 5: 129,219,574 (GRCm39) K465E probably benign Het
Aktip A T 8: 91,853,402 (GRCm39) V105E probably benign Het
Ankrd7 A G 6: 18,870,006 (GRCm39) Y253C probably damaging Het
Bag6 T C 17: 35,361,041 (GRCm39) M440T unknown Het
Camk2b T A 11: 5,922,838 (GRCm39) N426Y probably damaging Het
Ccdc82 T A 9: 13,289,706 (GRCm39) Y500* probably null Het
Cenpe T A 3: 134,930,777 (GRCm39) D341E probably damaging Het
Cyp2j13 A T 4: 95,956,428 (GRCm39) M227K probably benign Het
Dmbt1 G A 7: 130,692,134 (GRCm39) V967I unknown Het
Dtl A T 1: 191,285,175 (GRCm39) Y320* probably null Het
Dtymk A C 1: 93,729,543 (GRCm39) S3A probably benign Het
Eefsec G A 6: 88,423,253 (GRCm39) T70M possibly damaging Het
Fam171a1 C T 2: 3,221,344 (GRCm39) T270M probably damaging Het
Gm17728 T C 17: 9,641,159 (GRCm39) S90P probably benign Het
Hdlbp A G 1: 93,359,053 (GRCm39) L213P probably damaging Het
Heatr5b T C 17: 79,109,188 (GRCm39) I1024V probably benign Het
Hr C T 14: 70,799,305 (GRCm39) R597* probably null Het
Ifit3 T C 19: 34,564,988 (GRCm39) I178T probably damaging Het
Ifna6 A G 4: 88,746,222 (GRCm39) *190W probably null Het
Igkv4-55 A T 6: 69,584,315 (GRCm39) M99K probably benign Het
Klk1 T A 7: 43,877,056 (GRCm39) I53N probably damaging Het
Lpcat2b A G 5: 107,580,692 (GRCm39) H7R probably benign Het
Lrrc37a G A 11: 103,393,481 (GRCm39) P648L Het
Mast4 G T 13: 102,895,174 (GRCm39) P975H probably damaging Het
Mfrp C T 9: 44,013,807 (GRCm39) L106F probably benign Het
Mllt10 T A 2: 18,201,469 (GRCm39) S652T probably benign Het
Mroh8 C A 2: 157,083,673 (GRCm39) G400W probably damaging Het
Neurl4 A G 11: 69,794,788 (GRCm39) probably benign Het
Nop14 A C 5: 34,817,352 (GRCm39) V13G probably benign Het
Nup188 T A 2: 30,217,576 (GRCm39) L837Q probably damaging Het
Or2a54 T A 6: 43,092,905 (GRCm39) N76K possibly damaging Het
Or2ak5 T A 11: 58,611,572 (GRCm39) T101S probably benign Het
Or7g30 T C 9: 19,352,817 (GRCm39) S203P probably damaging Het
Or8k39 T C 2: 86,563,302 (GRCm39) Y218C probably damaging Het
Pate10 A G 9: 35,652,391 (GRCm39) Y16C probably damaging Het
Pde8b A T 13: 95,226,793 (GRCm39) V185E probably benign Het
Pink1 G T 4: 138,047,333 (GRCm39) A247D probably damaging Het
Pla2g10 A T 16: 13,545,914 (GRCm39) V40D probably damaging Het
Plce1 G A 19: 38,512,811 (GRCm39) G37R probably benign Het
Pld1 A G 3: 28,166,439 (GRCm39) E826G possibly damaging Het
Poc5 G T 13: 96,535,228 (GRCm39) K164N possibly damaging Het
Polr2b A T 5: 77,463,761 (GRCm39) M53L probably benign Het
Ppp1r10 C T 17: 36,239,690 (GRCm39) P470S probably damaging Het
Rasef A G 4: 73,645,840 (GRCm39) S510P probably damaging Het
Rnf17 T A 14: 56,722,658 (GRCm39) L1073Q probably damaging Het
Rpl13a-ps1 C T 19: 50,018,739 (GRCm39) G146R probably damaging Het
Scn2a A G 2: 65,518,730 (GRCm39) D368G probably damaging Het
Shc3 T A 13: 51,634,248 (GRCm39) S86C probably benign Het
Sos1 T C 17: 80,741,405 (GRCm39) H460R probably damaging Het
Steap1 T A 5: 5,790,838 (GRCm39) M37L probably benign Het
Themis G T 10: 28,673,492 (GRCm39) C593F possibly damaging Het
Tnn A G 1: 159,937,814 (GRCm39) probably null Het
Trabd G T 15: 88,969,667 (GRCm39) probably benign Het
Trim42 T A 9: 97,248,047 (GRCm39) K216N probably damaging Het
Trmt44 G A 5: 35,721,673 (GRCm39) P497S probably benign Het
Trp53bp2 A G 1: 182,256,475 (GRCm39) Y15C probably damaging Het
Trpm7 T A 2: 126,652,100 (GRCm39) I1458L probably benign Het
Ttc17 G T 2: 94,237,003 (GRCm39) A3E possibly damaging Het
Ttn C A 2: 76,704,208 (GRCm39) V9274L unknown Het
Tut7 T A 13: 59,937,011 (GRCm39) Q1212L possibly damaging Het
Vmn2r105 T A 17: 20,428,872 (GRCm39) I735F probably damaging Het
Vmn2r22 A G 6: 123,614,454 (GRCm39) C379R probably damaging Het
Vmn2r97 G A 17: 19,149,607 (GRCm39) E332K probably benign Het
Xrn1 A G 9: 95,920,732 (GRCm39) T1331A 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
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
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'- ATATTTTGCTCCCTGACAAACGTC -3'
(R):5'- AGGGCCTTCTCTGCTATAGC -3'

Sequencing Primer
(F):5'- CTGACAAACGTCCTATTTTGTTGG -3'
(R):5'- TATAGCACCTGTCCCTCAAACAG -3'
Posted On 2021-07-15