rs17653265
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_000165.5(GJA1):c.758C>T(p.Ala253Val) variant causes a missense change. The variant allele was found at a frequency of 0.0132 in 1,613,562 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000165.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJA1 | NM_000165.5 | c.758C>T | p.Ala253Val | missense_variant | Exon 2 of 2 | ENST00000282561.4 | NP_000156.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GJA1 | ENST00000282561.4 | c.758C>T | p.Ala253Val | missense_variant | Exon 2 of 2 | 1 | NM_000165.5 | ENSP00000282561.3 | ||
GJA1 | ENST00000647564.1 | c.758C>T | p.Ala253Val | missense_variant | Exon 2 of 2 | ENSP00000497565.1 | ||||
GJA1 | ENST00000649003.1 | c.758C>T | p.Ala253Val | missense_variant | Exon 2 of 2 | ENSP00000497283.1 | ||||
GJA1 | ENST00000650427.1 | c.758C>T | p.Ala253Val | missense_variant | Exon 2 of 2 | ENSP00000497367.1 |
Frequencies
GnomAD3 genomes AF: 0.00915 AC: 1388AN: 151664Hom.: 10 Cov.: 32
GnomAD3 exomes AF: 0.00809 AC: 2035AN: 251464Hom.: 23 AF XY: 0.00823 AC XY: 1119AN XY: 135906
GnomAD4 exome AF: 0.0136 AC: 19895AN: 1461780Hom.: 199 Cov.: 33 AF XY: 0.0133 AC XY: 9690AN XY: 727196
GnomAD4 genome AF: 0.00912 AC: 1384AN: 151782Hom.: 10 Cov.: 32 AF XY: 0.00832 AC XY: 617AN XY: 74162
ClinVar
Submissions by phenotype
not specified Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:3
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GJA1: PM5, BS1, BS2 -
Oculodentodigital dysplasia Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Oculodentodigital dysplasia, autosomal recessive Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at