rs200714519
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006514.4(SCN10A):c.1534C>T(p.Arg512*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,612,932 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 Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006514.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.1534C>T | p.Arg512* | stop_gained | 12/28 | 1 | NM_006514.4 | ENSP00000390600.2 | ||
SCN10A | ENST00000643924.1 | c.1534C>T | p.Arg512* | stop_gained | 11/27 | ENSP00000495595.1 | ||||
SCN10A | ENST00000655275.1 | c.1561C>T | p.Arg521* | stop_gained | 12/28 | ENSP00000499510.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249332Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134764
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1460674Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 39AN XY: 726576
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74440
ClinVar
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 13, 2022 | This sequence change creates a premature translational stop signal (p.Arg512*) in the SCN10A gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SCN10A cause disease. This variant is present in population databases (rs200714519, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of SCN10A-related conditions (PMID: 34385907). ClinVar contains an entry for this variant (Variation ID: 809464). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2024 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 14, 2022 | The p.R512* variant (also known as c.1534C>T), located in coding exon 11 of the SCN10A gene, results from a C to T substitution at nucleotide position 1534. This changes the amino acid from an arginine to a stop codon within coding exon 11. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of SCN10A has not been clearly established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at