rs6771157

Positions:

Variant summary

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

The NM_006514.4(SCN10A):c.3393C>G(p.Thr1131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,744 control chromosomes in the GnomAD database, including 51,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4092 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47339 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.553

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=-0.87).

BP6

Variant 3-38722372-G-C is Benign according to our data. Variant chr3-38722372-G-C is described in ClinVar as [Benign]. Clinvar id is 259998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38722372-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.553 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4 linkuse as main transcript	c.3393C>G	p.Thr1131=	synonymous_variant	20/28	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SCN10A	ENST00000449082.3 linkuse as main transcript	c.3393C>G	p.Thr1131=	synonymous_variant	20/28	1	NM_006514.4	ENSP00000390600	P4
SCN10A	ENST00000655275.1 linkuse as main transcript	c.3417C>G	p.Thr1139=	synonymous_variant	20/28			ENSP00000499510
SCN10A	ENST00000643924.1 linkuse as main transcript	c.3390C>G	p.Thr1130=	synonymous_variant	19/27			ENSP00000495595	A1

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33546

AN:

151952

Hom.:

4092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.239

AC:

60154

AN:

251362

Hom.:

7888

AF XY:

0.244

AC XY:

33159

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.388

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.250

AC:

365387

AN:

1461674

Hom.:

47339

Cov.:

AF XY:

0.250

AC XY:

181821

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.332

Gnomad4 EAS exome

AF:

0.437

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.221

AC:

33555

AN:

152070

Hom.:

4092

Cov.:

AF XY:

0.223

AC XY:

16542

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.255

Hom.:

1746

Bravo

AF:

0.208

Asia WGS

AF:

0.272

AC:

947

AN:

3478

EpiCase

AF:

0.247

EpiControl

AF:

0.248

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Episodic pain syndrome, familial, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

-0.87

CADD

Benign

0.57

DANN

Benign

0.28

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