rs79184444
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2
The NM_001349253.2(SCN11A):c.5063C>T(p.Ala1688Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,614,078 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1688S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001349253.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN11A | NM_001349253.2 | c.5063C>T | p.Ala1688Val | missense_variant | 30/30 | ENST00000302328.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN11A | ENST00000302328.9 | c.5063C>T | p.Ala1688Val | missense_variant | 30/30 | 5 | NM_001349253.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250880Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135566
GnomAD4 exome AF: 0.000107 AC: 156AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000949 AC XY: 69AN XY: 727242
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74414
ClinVar
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 7;C3809899:Familial episodic pain syndrome with predominantly lower limb involvement Uncertain:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 04-02-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1688 of the SCN11A protein (p.Ala1688Val). This variant is present in population databases (rs79184444, gnomAD 0.008%). This missense change has been observed in individual(s) with SCN11A-related conditions (Invitae). This missense change has been observed in at least one individual who was not affected with SCN11A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 474742). 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 SCN11A protein function with a positive predictive value of 80%. 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
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 05, 2021 | 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