chr21-44250870-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_175867.3(DNMT3L):c.849G>A(p.Met283Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 0)
Consequence
DNMT3L
NM_175867.3 missense
NM_175867.3 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.0660
Publications
0 publications found
Genes affected
DNMT3L (HGNC:2980): (DNA methyltransferase 3 like) 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 nuclear protein with similarity to DNA methyltransferases, but is not thought to function as a DNA methyltransferase as it does not contain the amino acid residues necessary for methyltransferase activity. However, it does stimulate de novo methylation by DNA cytosine methyltransferase 3 alpha and is thought to be required for the establishment of maternal genomic imprints. This protein also mediates transcriptional repression through interaction with histone deacetylase 1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.1571149).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_175867.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNMT3L | TSL:1 MANE Select | c.849G>A | p.Met283Ile | missense | Exon 10 of 12 | ENSP00000486001.1 | Q9UJW3-1 | ||
| DNMT3L | TSL:1 | c.849G>A | p.Met283Ile | missense | Exon 10 of 12 | ENSP00000270172.3 | Q9UJW3-2 | ||
| DNMT3L | TSL:5 | c.804G>A | p.Met268Ile | missense | Exon 9 of 9 | ENSP00000400242.1 | C9J0T5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
0
GnomAD2 exomes AF: 0.0000240 AC: 6AN: 250512 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
6
AN:
250512
AF XY:
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GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome
GnomAD4 genome
Cov.:
0
Alfa
AF:
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ExAC
AF:
AC:
3
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at L288 (P = 0.0691)
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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