rs78555408
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2
The NM_006514.4(SCN10A):āc.1157T>Gā(p.Phe386Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,614,206 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 32)
Exomes š: 0.00020 ( 1 hom. )
Consequence
SCN10A
NM_006514.4 missense
NM_006514.4 missense
Scores
15
1
2
Clinical Significance
Conservation
PhyloP100: 9.32
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 Benign. Variant got -15 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 11: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.041530877).
BP6
?
Variant 3-38756807-A-C is Benign according to our data. Variant chr3-38756807-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 240661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38756807-A-C is described in Lovd as [Benign].
BS2
?
High AC in GnomAd4 at 30 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.1157T>G | p.Phe386Cys | missense_variant | 10/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.1157T>G | p.Phe386Cys | missense_variant | 10/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.1184T>G | p.Phe395Cys | missense_variant | 10/28 | ||||
SCN10A | ENST00000643924.1 | c.1157T>G | p.Phe386Cys | missense_variant | 9/27 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000513 AC: 129AN: 251388Hom.: 0 AF XY: 0.000486 AC XY: 66AN XY: 135850
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GnomAD4 exome AF: 0.000201 AC: 294AN: 1461888Hom.: 1 Cov.: 32 AF XY: 0.000204 AC XY: 148AN XY: 727244
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GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Brugada syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2020 | Reported in association with ventricular tachycardia and/or ventricular fibrillation, sudden unexplained nocturnal death syndrome, and Brugada syndrome, although at least one of the reported probands was found to harbor an additional cardiogenetic variant (Hu et al., 2014; Zhang et al., 2017); This variant is associated with the following publications: (PMID: 30821013, 27272739, 24998131) - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 16, 2019 | 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;H;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.
Sift4G
Pathogenic
D;.;.;.
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