rs776213428
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001037.5(SCN1B):c.523G>A(p.Val175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,146 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V175L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001037.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.523G>A | p.Val175Met | missense_variant | 4/6 | ENST00000262631.11 | |
SCN1B | NM_001321605.2 | c.424G>A | p.Val142Met | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1B | ENST00000262631.11 | c.523G>A | p.Val175Met | missense_variant | 4/6 | 1 | NM_001037.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251078Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135764
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727218
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74490
ClinVar
Submissions by phenotype
Brugada syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | The SCN1B gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001037.5, and corresponds to NM_199037.4:c.*5093G>A in the primary transcript. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 175 of the SCN1B protein (p.Val175Met). This variant is present in population databases (rs776213428, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | The c.523G>A (p.V175M) alteration is located in exon 4 (coding exon 4) of the SCN1B gene. This alteration results from a G to A substitution at nucleotide position 523, causing the valine (V) at amino acid position 175 to be replaced by a methionine (M). The p.V175M alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at