rs770694096
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_000334.4(SCN4A):c.2419G>A(p.Ala807Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000456 in 1,557,192 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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. A807V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN4A | NM_000334.4 | c.2419G>A | p.Ala807Thr | missense_variant | 14/24 | ENST00000435607.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN4A | ENST00000435607.3 | c.2419G>A | p.Ala807Thr | missense_variant | 14/24 | 1 | NM_000334.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000652 AC: 11AN: 168716Hom.: 0 AF XY: 0.0000876 AC XY: 8AN XY: 91342
GnomAD4 exome AF: 0.0000448 AC: 63AN: 1404944Hom.: 1 Cov.: 32 AF XY: 0.0000576 AC XY: 40AN XY: 693890
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74438
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 20, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 12, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2023 | The c.2419G>A (p.A807T) alteration is located in exon 14 (coding exon 14) of the SCN4A gene. This alteration results from a G to A substitution at nucleotide position 2419, causing the alanine (A) at amino acid position 807 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hyperkalemic periodic paralysis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 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 not expected to disrupt SCN4A protein function. ClinVar contains an entry for this variant (Variation ID: 572594). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. This variant is present in population databases (rs770694096, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 807 of the SCN4A protein (p.Ala807Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at