3-38725210-C-T

Position:

chr3-38725210-C-T

Variant summary

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

The NM_006514.4(SCN10A):c.3192G>A(p.Thr1064=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,604,944 control chromosomes in the GnomAD database, including 17,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1926 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15487 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0480

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=-0.67).

BP6

Variant 3-38725210-C-T is Benign according to our data. Variant chr3-38725210-C-T is described in ClinVar as [Benign]. Clinvar id is 259995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38725210-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.048 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 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.3192G>A	p.Thr1064=	synonymous_variant	18/28	ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCN10A	ENST00000449082.3 linkuse as main transcript	c.3192G>A	p.Thr1064=	synonymous_variant	18/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1 linkuse as main transcript	c.3216G>A	p.Thr1072=	synonymous_variant	18/28
SCN10A	ENST00000643924.1 linkuse as main transcript	c.3189G>A	p.Thr1063=	synonymous_variant	17/27			A1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22984

AN:

152092

Hom.:

1927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0839

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.121

AC:

30330

AN:

249642

Hom.:

2130

AF XY:

0.119

AC XY:

16050

AN XY:

134964

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.0873

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.0862

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.141

AC:

205526

AN:

1452734

Hom.:

15487

Cov.:

AF XY:

0.139

AC XY:

100690

AN XY:

721916

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.0869

Gnomad4 EAS exome

AF:

0.00121

Gnomad4 SAS exome

AF:

0.0846

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.154

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.151

AC:

22995

AN:

152210

Hom.:

1926

Cov.:

AF XY:

0.146

AC XY:

10906

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.0914

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0835

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.144

Hom.:

2698

Bravo

AF:

0.156

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

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, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 26, 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	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	Jun 10, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 2023	- -

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

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 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

-0.67

CADD

Benign

5.4

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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