rs141810266
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_006514.4(SCN10A):c.55G>A(p.Glu19Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000874 in 1,613,900 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 1 hom. )
Consequence
SCN10A
NM_006514.4 missense
NM_006514.4 missense
Scores
7
7
4
Clinical Significance
Conservation
PhyloP100: 6.12
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36074215).
BP6
?
Variant 3-38793956-C-T is Benign according to our data. Variant chr3-38793956-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 414620.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS2
?
High AC in GnomAd4 at 75 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.55G>A | p.Glu19Lys | missense_variant | 2/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.55G>A | p.Glu19Lys | missense_variant | 2/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.55G>A | p.Glu19Lys | missense_variant | 2/28 | ||||
SCN10A | ENST00000643924.1 | c.55G>A | p.Glu19Lys | missense_variant | 1/27 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000493 AC: 75AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000120 AC: 30AN: 250884Hom.: 0 AF XY: 0.0000959 AC XY: 13AN XY: 135550
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GnomAD4 exome AF: 0.0000452 AC: 66AN: 1461728Hom.: 1 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727168
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GnomAD4 genome ? AF: 0.000493 AC: 75AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36AN XY: 74334
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2023 | Published in one individual with Brugada syndrome (Behr et al., 2015); however, no clinical details or segregation data were provided; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing; however, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 29037745, 25691538, 30821013) - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 26, 2020 | This alteration is classified as likely 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.;.
Sift4G
Uncertain
T;.;.;.
Polyphen
D;.;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at