rs141648641
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_006514.4(SCN10A):c.5605C>T(p.Arg1869Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 1,614,112 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1869H) has been classified as Uncertain significance.
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.5605C>T | p.Arg1869Cys | missense_variant | 28/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.5605C>T | p.Arg1869Cys | missense_variant | 28/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.5629C>T | p.Arg1877Cys | missense_variant | 28/28 | ||||
SCN10A | ENST00000643924.1 | c.5602C>T | p.Arg1868Cys | missense_variant | 27/27 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000585 AC: 89AN: 152158Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000999 AC: 251AN: 251126Hom.: 2 AF XY: 0.000899 AC XY: 122AN XY: 135700
GnomAD4 exome AF: 0.000527 AC: 770AN: 1461836Hom.: 7 Cov.: 32 AF XY: 0.000557 AC XY: 405AN XY: 727226
GnomAD4 genome AF: 0.000584 AC: 89AN: 152276Hom.: 2 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74448
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | SCN10A: BS1 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2019 | This variant is associated with the following publications: (PMID: 27711072, 26733327, 24998131, 29016797, 30821013, 32948286) - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at