3-38698354-A-G

Position:

chr3-38698354-A-G

Variant summary

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

The NM_006514.4(SCN10A):c.4866T>C(p.Ser1622=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 1,614,070 control chromosomes in the GnomAD database, including 675,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66000 hom., cov: 30)

Exomes 𝑓: 0.91 ( 609773 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.831

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=-0.54).

BP6

Variant 3-38698354-A-G is Benign according to our data. Variant chr3-38698354-A-G is described in ClinVar as [Benign]. Clinvar id is 95404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38698354-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.831 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4 linkuse as main transcript	c.4866T>C	p.Ser1622=	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.4866T>C	p.Ser1622=	synonymous_variant	28/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1 linkuse as main transcript	c.4890T>C	p.Ser1630=	synonymous_variant	28/28
SCN10A	ENST00000643924.1 linkuse as main transcript	c.4863T>C	p.Ser1621=	synonymous_variant	27/27			A1

Frequencies

GnomAD3 genomes

AF:

0.931

AC:

141560

AN:

152060

Hom.:

65940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.941

Gnomad EAS

AF:

0.963

Gnomad SAS

AF:

0.876

Gnomad FIN

AF:

0.936

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.915

Gnomad OTH

AF:

0.932

GnomAD3 exomes

AF:

0.920

AC:

231246

AN:

251356

Hom.:

106493

AF XY:

0.917

AC XY:

124627

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.961

Gnomad AMR exome

AF:

0.914

Gnomad ASJ exome

AF:

0.943

Gnomad EAS exome

AF:

0.969

Gnomad SAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.935

Gnomad NFE exome

AF:

0.916

Gnomad OTH exome

AF:

0.922

GnomAD4 exome

AF:

0.913

AC:

1334834

AN:

1461892

Hom.:

609773

Cov.:

AF XY:

0.912

AC XY:

663209

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.962

Gnomad4 AMR exome

AF:

0.916

Gnomad4 ASJ exome

AF:

0.943

Gnomad4 EAS exome

AF:

0.963

Gnomad4 SAS exome

AF:

0.879

Gnomad4 FIN exome

AF:

0.931

Gnomad4 NFE exome

AF:

0.911

Gnomad4 OTH exome

AF:

0.914

GnomAD4 genome

AF:

0.931

AC:

141679

AN:

152178

Hom.:

66000

Cov.:

AF XY:

0.932

AC XY:

69290

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.961

Gnomad4 AMR

AF:

0.921

Gnomad4 ASJ

AF:

0.941

Gnomad4 EAS

AF:

0.963

Gnomad4 SAS

AF:

0.876

Gnomad4 FIN

AF:

0.936

Gnomad4 NFE

AF:

0.915

Gnomad4 OTH

AF:

0.933

Alfa

AF:

0.922

Hom.:

75555

Bravo

AF:

0.932

Asia WGS

AF:

0.905

AC:

3150

AN:

3478

EpiCase

AF:

0.917

EpiControl

AF:

0.922

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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	Eurofins Ntd Llc (ga)	Jul 05, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	Jun 10, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 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. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -

Episodic pain syndrome, familial, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 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

-0.54

CADD

Benign

7.2

DANN

Benign

0.73

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