rs144944369

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_006514.4(SCN10A):c.4416C>T(p.Ile1472Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,572,562 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0620

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 -15 ACMG points.

BP4

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

BP6

Variant 3-38702080-G-A is Benign according to our data. Variant chr3-38702080-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38702080-G-A is described in Lovd as [Benign]. Variant chr3-38702080-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.062 with no splicing effect.

BS2

High AC in GnomAd4 at 219 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4 link	c.4416C>T	p.Ile1472Ile	synonymous_variant	Exon 27 of 28	ENST00000449082.3	NP_006505.4	Q9Y5Y9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN10A	ENST00000449082.3 link	c.4416C>T	p.Ile1472Ile	synonymous_variant	Exon 27 of 28	1	NM_006514.4	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1 link	c.4413C>T	p.Ile1471Ile	synonymous_variant	Exon 26 of 27			ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1 link	c.4440C>T	p.Ile1480Ile	synonymous_variant	Exon 27 of 28			ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00204

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00106

AC:

229

AN:

215072

Hom.:

AF XY:

0.000982

AC XY:

113

AN XY:

115082

show subpopulations

Gnomad AFR exome

AF:

0.000896

Gnomad AMR exome

AF:

0.000431

Gnomad ASJ exome

AF:

0.000139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000931

Gnomad FIN exome

AF:

0.00161

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00103

AC:

1466

AN:

1420240

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

729

AN XY:

702332

show subpopulations

Gnomad4 AFR exome

AF:

0.000376

Gnomad4 AMR exome

AF:

0.000545

Gnomad4 ASJ exome

AF:

0.000126

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00153

Gnomad4 NFE exome

AF:

0.00118

Gnomad4 OTH exome

AF:

0.000905

GnomAD4 genome

AF:

0.00144

AC:

219

AN:

152322

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00204

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00111

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Dec 28, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SCN10A: BP4, BP7, BS1 -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Episodic pain syndrome, familial, 2

Benign:1

Jul 26, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brugada syndrome

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Mar 20, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.39

CADD

Benign

4.6

DANN

Benign

0.67

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