rs782438073
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_181703.4(GJA5):c.430G>A(p.Ala144Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A144A) has been classified as Likely benign.
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.430G>A | p.Ala144Thr | missense_variant | 2/2 | ENST00000579774.3 | |
LOC102723321 | XR_922079.4 | n.82-18752C>T | intron_variant, non_coding_transcript_variant | ||||
GJA5 | NM_005266.7 | c.430G>A | p.Ala144Thr | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJA5 | ENST00000579774.3 | c.430G>A | p.Ala144Thr | missense_variant | 2/2 | 1 | NM_181703.4 | P1 | |
GJA5 | ENST00000621517.1 | c.430G>A | p.Ala144Thr | missense_variant | 2/2 | 2 | P1 | ||
GJA5 | ENST00000430508.1 | c.430G>A | p.Ala144Thr | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250748Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135534
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461858Hom.: 0 Cov.: 33 AF XY: 0.0000316 AC XY: 23AN XY: 727234
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 11;C4551959:Atrial standstill 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 06, 2023 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GJA5 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 567064). This variant has not been reported in the literature in individuals affected with GJA5-related conditions. This variant is present in population databases (rs782438073, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 144 of the GJA5 protein (p.Ala144Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at