rs121908592
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2
The NM_002234.4(KCNA5):c.1727C>T(p.Ala576Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002234.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250902Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135704
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461792Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727198
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 7 Pathogenic:2Uncertain:1
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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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 13471). This missense change has been observed in individual(s) with atrial fibrillation and/or pulmonary arterial hypertension (PMID: 19343045, 31727138). This variant is present in population databases (rs121908592, gnomAD 0.05%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 576 of the KCNA5 protein (p.Ala576Val). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at