rs782065420
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_181703.4(GJA5):c.496G>A(p.Gly166Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G166A) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJA5 | NM_181703.4 | c.496G>A | p.Gly166Ser | missense_variant | 2/2 | ENST00000579774.3 | |
LOC102723321 | XR_922079.4 | n.82-18818C>T | intron_variant, non_coding_transcript_variant | ||||
GJA5 | NM_005266.7 | c.496G>A | p.Gly166Ser | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJA5 | ENST00000579774.3 | c.496G>A | p.Gly166Ser | missense_variant | 2/2 | 1 | NM_181703.4 | P1 | |
GJA5 | ENST00000621517.1 | c.496G>A | p.Gly166Ser | missense_variant | 2/2 | 2 | P1 | ||
GJA5 | ENST00000430508.1 | c.496G>A | p.Gly166Ser | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250762Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135496
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461816Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 727224
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 06, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2021 | 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); At the protein level, in silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 577850; Landrum et al., 2016) - |
Atrial fibrillation, familial, 11;C4551959:Atrial standstill 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 11, 2018 | This sequence change replaces glycine with serine at codon 166 of the GJA5 protein (p.Gly166Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs782065420, ExAC 0.002%). This variant has not been reported in the literature in individuals with GJA5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at