3-38756680-C-T

Position:

chr3-38756680-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006514.4(SCN10A):c.1284G>A(p.Glu428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,192 control chromosomes in the GnomAD database, including 47,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3662 hom., cov: 31)

Exomes 𝑓: 0.24 ( 44038 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.490

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 3-38756680-C-T is Benign according to our data. Variant chr3-38756680-C-T is described in ClinVar as [Benign]. Clinvar id is 259991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38756680-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 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.1284G>A	p.Glu428=	synonymous_variant	10/28	ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCN10A	ENST00000449082.3 linkuse as main transcript	c.1284G>A	p.Glu428=	synonymous_variant	10/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1 linkuse as main transcript	c.1311G>A	p.Glu437=	synonymous_variant	10/28
SCN10A	ENST00000643924.1 linkuse as main transcript	c.1284G>A	p.Glu428=	synonymous_variant	9/27			A1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31127

AN:

151958

Hom.:

3662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.231

AC:

57831

AN:

250870

Hom.:

7487

AF XY:

0.236

AC XY:

32015

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.240

AC:

350749

AN:

1460116

Hom.:

44038

Cov.:

AF XY:

0.241

AC XY:

174949

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.327

Gnomad4 EAS exome

AF:

0.427

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.241

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.205

AC:

31130

AN:

152076

Hom.:

3662

Cov.:

AF XY:

0.206

AC XY:

15315

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.244

Hom.:

2366

Bravo

AF:

0.192

Asia WGS

AF:

0.270

AC:

940

AN:

3478

EpiCase

AF:

0.238

EpiControl

AF:

0.239

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	Jun 17, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 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, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 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 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

-0.39

CADD

Benign

3.2

DANN

Benign

0.48

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