rs750424299
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_000890.5(KCNJ5):c.616G>A(p.Ala206Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,609,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A206A) has been classified as Likely benign.
Frequency
Consequence
NM_000890.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ5 | NM_000890.5 | c.616G>A | p.Ala206Thr | missense_variant | 2/3 | ENST00000529694.6 | |
KCNJ5 | NM_001354169.2 | c.616G>A | p.Ala206Thr | missense_variant | 3/4 | ||
KCNJ5 | XM_011542810.4 | c.616G>A | p.Ala206Thr | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ5 | ENST00000529694.6 | c.616G>A | p.Ala206Thr | missense_variant | 2/3 | 1 | NM_000890.5 | P1 | |
KCNJ5 | ENST00000338350.4 | c.616G>A | p.Ala206Thr | missense_variant | 3/4 | 1 | P1 | ||
KCNJ5 | ENST00000533599.1 | c.616G>A | p.Ala206Thr | missense_variant | 1/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250780Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135494
GnomAD4 exome AF: 0.00000892 AC: 13AN: 1457664Hom.: 0 Cov.: 59 AF XY: 0.0000138 AC XY: 10AN XY: 724198
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74312
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2023 | 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. 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 expected to disrupt KCNJ5 protein function. ClinVar contains an entry for this variant (Variation ID: 427972). This variant has not been reported in the literature in individuals affected with KCNJ5-related conditions. This variant is present in population databases (rs750424299, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 206 of the KCNJ5 protein (p.Ala206Thr). - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Human Genetics, University of Leuven | Apr 30, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at