rs116353929

Positions:

chr3-38698003-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006514.4(SCN10A):c.5217C>T(p.Asp1739=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 1,614,122 control chromosomes in the GnomAD database, including 861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 44 hom., cov: 32)

Exomes 𝑓: 0.031 ( 817 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.285

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=-0.82).

BP6

Variant 3-38698003-G-A is Benign according to our data. Variant chr3-38698003-G-A is described in ClinVar as [Benign]. Clinvar id is 240680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38698003-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.285 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0225 (3428/152244) while in subpopulation NFE AF= 0.0329 (2237/68014). AF 95% confidence interval is 0.0318. There are 44 homozygotes in gnomad4. There are 1635 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3428 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4 linkuse as main transcript	c.5217C>T	p.Asp1739=	synonymous_variant	28/28	ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCN10A	ENST00000449082.3 linkuse as main transcript	c.5217C>T	p.Asp1739=	synonymous_variant	28/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1 linkuse as main transcript	c.5241C>T	p.Asp1747=	synonymous_variant	28/28
SCN10A	ENST00000643924.1 linkuse as main transcript	c.5214C>T	p.Asp1738=	synonymous_variant	27/27			A1

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3426

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0251

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0329

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0263

AC:

6610

AN:

251198

Hom.:

103

AF XY:

0.0267

AC XY:

3628

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00547

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0286

Gnomad FIN exome

AF:

0.0251

Gnomad NFE exome

AF:

0.0316

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0315

AC:

46038

AN:

1461878

Hom.:

817

Cov.:

AF XY:

0.0316

AC XY:

22974

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00523

Gnomad4 AMR exome

AF:

0.0309

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.000982

Gnomad4 SAS exome

AF:

0.0300

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0347

Gnomad4 OTH exome

AF:

0.0263

GnomAD4 genome

AF:

0.0225

AC:

3428

AN:

152244

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

1635

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00590

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0291

Gnomad4 FIN

AF:

0.0251

Gnomad4 NFE

AF:

0.0329

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0225

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0325

EpiControl

AF:

0.0296

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	Jun 10, 2016	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2016	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. -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2018

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

-0.82

CADD

Benign

0.013

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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