chr2-165090728-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4BP6BS1BS2
The NM_006922.4(SCN3A):c.5425G>A(p.Glu1809Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E1809E) has been classified as Likely benign.
Frequency
Consequence
NM_006922.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251382Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135862
GnomAD4 exome AF: 0.000228 AC: 334AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.000217 AC XY: 158AN XY: 727230
GnomAD4 genome AF: 0.000151 AC: 23AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74278
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1809 of the SCN3A protein (p.Glu1809Lys). This variant is present in population databases (rs370463938, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SCN3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 403875). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SCN3A protein function with a negative predictive value of 95%. 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. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at