Variant rs148905110 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006514.4(SCN10A):c.1713G>A(p.Pro571=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,572,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.72

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-38752261-C-T is Benign according to our data. Variant chr3-38752261-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.72 with no splicing effect.

BS2

High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4 linkuse as main transcript	c.1713G>A	p.Pro571=	synonymous_variant	12/28	ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCN10A	ENST00000449082.3 linkuse as main transcript	c.1713G>A	p.Pro571=	synonymous_variant	12/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1 linkuse as main transcript	c.1740G>A	p.Pro580=	synonymous_variant	12/28
SCN10A	ENST00000643924.1 linkuse as main transcript	c.1713G>A	p.Pro571=	synonymous_variant	11/27			A1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151706

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000241

AC:

AN:

219666

Hom.:

AF XY:

0.000286

AC XY:

AN XY:

118804

show subpopulations

Gnomad AFR exome

AF:

0.0000674

Gnomad AMR exome

AF:

0.0000677

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000633

Gnomad SAS exome

AF:

0.000198

Gnomad FIN exome

AF:

0.000245

Gnomad NFE exome

AF:

0.000386

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000589

AC:

836

AN:

1420544

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

417

AN XY:

704284

show subpopulations

Gnomad4 AFR exome

AF:

0.0000629

Gnomad4 AMR exome

AF:

0.000124

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.0000997

Gnomad4 FIN exome

AF:

0.000153

Gnomad4 NFE exome

AF:

0.000722

Gnomad4 OTH exome

AF:

0.000427

GnomAD4 genome

AF:

0.000277

AC:

AN:

151824

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000204

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SCN10A-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 13, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Brugada syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 18, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2018

- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2018

This alteration is classified as likely 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

-0.81

CADD

Benign

0.32

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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