rs7617919

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006514.4(SCN10A):c.1476C>T(p.Leu492Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,588,222 control chromosomes in the GnomAD database, including 47,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3705 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43642 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.20

Variant links:

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]

SCN10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-38752498-G-A is Benign according to our data. Variant chr3-38752498-G-A is described in ClinVar as [Benign]. Clinvar id is 259992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38752498-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4 link	c.1476C>T	p.Leu492Leu	synonymous_variant	Exon 12 of 28	ENST00000449082.3	NP_006505.4	Q9Y5Y9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN10A	ENST00000449082.3 link	c.1476C>T	p.Leu492Leu	synonymous_variant	Exon 12 of 28	1	NM_006514.4	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1 link	c.1476C>T	p.Leu492Leu	synonymous_variant	Exon 11 of 27			ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1 link	c.1503C>T	p.Leu501Leu	synonymous_variant	Exon 12 of 28			ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31307

AN:

152038

Hom.:

3705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.233

AC:

53412

AN:

229124

Hom.:

6923

AF XY:

0.239

AC XY:

29589

AN XY:

123944

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.389

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.241

AC:

346768

AN:

1436066

Hom.:

43642

Cov.:

AF XY:

0.242

AC XY:

172275

AN XY:

711868

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.206

AC:

31310

AN:

152156

Hom.:

3705

Cov.:

AF XY:

0.207

AC XY:

15411

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.233

Hom.:

5241

Bravo

AF:

0.193

Asia WGS

AF:

0.270

AC:

940

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 18, 2017

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 09, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 23, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Episodic pain syndrome, familial, 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brugada syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 21, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over