rs151182542

Positions:

chr3-38701840-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006514.4(SCN10A):c.4656G>A(p.Ala1552Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 1,597,466 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 6 hom. )

Consequence

SCN10A
NM_006514.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00003792

Clinical Significance

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

Conservation

PhyloP100: -2.40

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-38701840-C-T is Benign according to our data. Variant chr3-38701840-C-T is described in ClinVar as [Benign]. Clinvar id is 506666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38701840-C-T is described in Lovd as [Benign]. Variant chr3-38701840-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.4 with no splicing effect.

BS2

High AC in GnomAd4 at 622 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4 linkuse as main transcript	c.4656G>A	p.Ala1552Ala	splice_region_variant, synonymous_variant	27/28	ENST00000449082.3	NP_006505.4	Q9Y5Y9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCN10A	ENST00000449082.3 linkuse as main transcript	c.4656G>A	p.Ala1552Ala	splice_region_variant, synonymous_variant	27/28	1	NM_006514.4	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1 linkuse as main transcript	c.4653G>A	p.Ala1551Ala	splice_region_variant, synonymous_variant	26/27			ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1 linkuse as main transcript	c.4680G>A	p.Ala1560Ala	splice_region_variant, synonymous_variant	27/28			ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

619

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00118

AC:

284

AN:

239864

Hom.:

AF XY:

0.000990

AC XY:

128

AN XY:

129244

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.000554

Gnomad ASJ exome

AF:

0.000629

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000362

Gnomad FIN exome

AF:

0.0000471

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.000862

GnomAD4 exome

AF:

0.000537

AC:

776

AN:

1445112

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

364

AN XY:

716526

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.000948

Gnomad4 ASJ exome

AF:

0.000626

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00408

AC:

622

AN:

152354

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.000996

Hom.:

Bravo

AF:

0.00479

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 27, 2017	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	May 26, 2024	- -

not provided

Benign:3

Likely 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	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	SCN10A: BS1, BS2 -
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

Jan 19, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 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

1.8

DANN

Benign

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.098

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