rs774311301
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2PP3_ModerateBS2
The NM_004519.4(KCNQ3):c.1525G>A(p.Glu509Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,110 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 (★).
Frequency
Consequence
NM_004519.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000813 AC: 2AN: 245954Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133042
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1459110Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725778
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Benign neonatal seizures Uncertain:1
This sequence change replaces glutamic acid with lysine at codon 509 of the KCNQ3 protein (p.Glu509Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs774311301, ExAC 0.002%). 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCNQ3-related disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at