3-38697368-A-C
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006514.4(SCN10A):c.5852T>G(p.Leu1951Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L1951L) has been classified as Likely benign.
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
Publications
- sodium channelopathy-related small fiber neuropathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- episodic pain syndrome, familial, 2Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
- Brugada syndromeInheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp
- Brugada syndrome 1Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.5852T>G | p.Leu1951Arg | missense_variant | Exon 28 of 28 | 1 | NM_006514.4 | ENSP00000390600.2 | ||
SCN10A | ENST00000643924.1 | c.5849T>G | p.Leu1950Arg | missense_variant | Exon 27 of 27 | ENSP00000495595.1 | ||||
SCN10A | ENST00000655275.1 | c.5876T>G | p.Leu1959Arg | missense_variant | Exon 28 of 28 | ENSP00000499510.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
The p.L1951R variant (also known as c.5852T>G), located in coding exon 27 of the SCN10A gene, results from a T to G substitution at nucleotide position 5852. The leucine at codon 1951 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at