3-38698341-ACATACC-ATGGAGTAGAT
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006514.4(SCN10A):c.4873_4878delinsATCTACTCCA(p.Gly1625IlefsTer56) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G1625G) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Consequence
SCN10A
NM_006514.4 frameshift
NM_006514.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.31
Genes affected
SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.4873_4878delinsATCTACTCCA | p.Gly1625IlefsTer56 | frameshift_variant | 28/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.4873_4878delinsATCTACTCCA | p.Gly1625IlefsTer56 | frameshift_variant | 28/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000643924.1 | c.4870_4875delinsATCTACTCCA | p.Gly1624IlefsTer56 | frameshift_variant | 27/27 | A1 | |||
SCN10A | ENST00000655275.1 | c.4897_4902delinsATCTACTCCA | p.Gly1633IlefsTer56 | frameshift_variant | 28/28 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. This variant is present in population databases (rs759319080, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gly1625Ilefs*56) in the SCN10A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 332 amino acid(s) of the SCN10A protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at