rs782703462
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_181703.4(GJA5):c.977G>C(p.Gly326Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G326E) has been classified as Uncertain significance.
Frequency
Consequence
NM_181703.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJA5 | NM_181703.4 | c.977G>C | p.Gly326Ala | missense_variant | 2/2 | ENST00000579774.3 | |
LOC102723321 | XR_922079.4 | n.82-19299C>G | intron_variant, non_coding_transcript_variant | ||||
GJA5 | NM_005266.7 | c.977G>C | p.Gly326Ala | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJA5 | ENST00000579774.3 | c.977G>C | p.Gly326Ala | missense_variant | 2/2 | 1 | NM_181703.4 | P1 | |
ENST00000612401.1 | n.309-141C>G | intron_variant, non_coding_transcript_variant | 5 | ||||||
GJA5 | ENST00000621517.1 | c.977G>C | p.Gly326Ala | missense_variant | 2/2 | 2 | P1 | ||
ENST00000622634.1 | n.480-92C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251438Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135888
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461850Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727230
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 11;C4551959:Atrial standstill 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 326 of the GJA5 protein (p.Gly326Ala). This variant is present in population databases (rs782703462, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GJA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1316153). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance, but additional evidence is not available (ClinVar Variant ID# 566272; Landrum et al., 2016) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at