6-121446900-C-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000165.5(GJA1):c.53C>A(p.Ser18*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000165.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJA1 | NM_000165.5 | c.53C>A | p.Ser18* | stop_gained | 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.53C>A | p.Ser18* | stop_gained | Exon 2 of 2 | 1 | NM_000165.5 | ENSP00000282561.3 | ||
GJA1 | ENST00000647564.1 | c.53C>A | p.Ser18* | stop_gained | Exon 2 of 2 | ENSP00000497565.1 | ||||
GJA1 | ENST00000649003.1 | c.53C>A | p.Ser18* | stop_gained | Exon 2 of 2 | ENSP00000497283.1 | ||||
GJA1 | ENST00000650427.1 | c.53C>A | p.Ser18* | stop_gained | Exon 2 of 2 | ENSP00000497367.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Oculodentodigital dysplasia, autosomal recessive Pathogenic:1
This sequence change creates a premature translational stop signal (p.Ser18*) in the GJA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 365 amino acid(s) of the GJA1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive oculodentodigital dysplasia (internal data). ClinVar contains an entry for this variant (Variation ID: 941060). This variant disrupts a region of the GJA1 protein in which other variant(s) (p.Arg33*) have been determined to be pathogenic (PMID: 16816024, 23606748). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at