rs587778238

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_022552.5(DNMT3A):​c.645G>C​(p.Glu215Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

DNMT3A
NM_022552.5 missense

Scores

1
13
5

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 6.84
Variant links:
Genes affected
DNMT3A (HGNC:2978): (DNA methyltransferase 3 alpha) CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1
In a region_of_interest Interaction with DNMT1 and DNMT3B (size 204) in uniprot entity DNM3A_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_022552.5
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41372254).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNMT3ANM_022552.5 linkuse as main transcriptc.645G>C p.Glu215Asp missense_variant 7/23 ENST00000321117.10 NP_072046.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNMT3AENST00000321117.10 linkuse as main transcriptc.645G>C p.Glu215Asp missense_variant 7/231 NM_022552.5 ENSP00000324375 P3Q9Y6K1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;.;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.91
.;D;D
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.41
T;T;T
MetaSVM
Uncertain
0.56
D
MutationAssessor
Benign
2.0
M;.;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.74
N;N;N
REVEL
Uncertain
0.52
Sift
Uncertain
0.023
D;D;D
Sift4G
Benign
0.11
T;T;T
Polyphen
0.96
P;.;P
Vest4
0.42
MutPred
0.38
Loss of sheet (P = 0.0037);.;Loss of sheet (P = 0.0037);
MVP
0.86
MPC
1.1
ClinPred
0.77
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.32
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs587778238; hg19: chr2-25471116; API