rs12632942

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006514.4(SCN10A):c.3275T>C(p.Leu1092Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,611,844 control chromosomes in the GnomAD database, including 51,330 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4103 hom., cov: 33)

Exomes 𝑓: 0.25 ( 47227 hom. )

Consequence

SCN10A
NM_006514.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.776

Publications

58 publications found

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 Gene-Disease associations (from GenCC):

sodium channelopathy-related small fiber neuropathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
episodic pain syndrome, familial, 2
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
Brugada syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SCN10A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020908415).

BP6

Variant 3-38723507-A-G is Benign according to our data. Variant chr3-38723507-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4 link	c.3275T>C	p.Leu1092Pro	missense_variant	Exon 19 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.3275T>C	p.Leu1092Pro	missense_variant	Exon 19 of 28	1	NM_006514.4	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1 link	c.3272T>C	p.Leu1091Pro	missense_variant	Exon 18 of 27			ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1 link	c.3299T>C	p.Leu1100Pro	missense_variant	Exon 19 of 28			ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33587

AN:

152066

Hom.:

4103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.216

GnomAD2 exomes

AF:

0.240

AC:

58530

AN:

243924

AF XY:

0.245

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.389

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.250

AC:

364980

AN:

1459660

Hom.:

47227

Cov.:

AF XY:

0.250

AC XY:

181556

AN XY:

725990

show subpopulations

African (AFR)

AF:

0.130

AC:

4341

AN:

33460

American (AMR)

AF:

0.121

AC:

5363

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8663

AN:

26108

East Asian (EAS)

AF:

0.437

AC:

17309

AN:

39632

South Asian (SAS)

AF:

0.233

AC:

20050

AN:

85976

European-Finnish (FIN)

AF:

0.273

AC:

14535

AN:

53312

Middle Eastern (MID)

AF:

0.229

AC:

1318

AN:

5766

European-Non Finnish (NFE)

AF:

0.251

AC:

278670

AN:

1110636

Other (OTH)

AF:

0.244

AC:

14731

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

13815

27630

41444

55259

69074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9418

18836

28254

37672

47090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.221

AC:

33596

AN:

152184

Hom.:

4103

Cov.:

AF XY:

0.223

AC XY:

16583

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.138

AC:

5737

AN:

41540

American (AMR)

AF:

0.149

AC:

2279

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1183

AN:

3470

East Asian (EAS)

AF:

0.403

AC:

2085

AN:

5168

South Asian (SAS)

AF:

0.241

AC:

1159

AN:

4816

European-Finnish (FIN)

AF:

0.273

AC:

2894

AN:

10596

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17404

AN:

67978

Other (OTH)

AF:

0.214

AC:

452

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1368

2735

4103

5470

6838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.245

Hom.:

22171

Bravo

AF:

0.209

TwinsUK

AF:

0.250

AC:

926

ALSPAC

AF:

0.241

AC:

928

ESP6500AA

AF:

0.142

AC:

625

ESP6500EA

AF:

0.260

AC:

2236

ExAC

AF:

0.241

AC:

29298

Asia WGS

AF:

0.272

AC:

946

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 09, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

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:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 23, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jun 10, 2016

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Brugada syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Episodic pain syndrome, familial, 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 21, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.036

T;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.24

.;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.72

N;.;N;.

PhyloP100

-0.78

PrimateAI

Benign

0.30

PROVEAN

Benign

3.2

N;.;.;.

REVEL

Benign

0.18

Sift

Benign

0.60

T;.;.;.

Sift4G

Benign

0.41

T;.;.;.

Polyphen

0.0

B;.;B;.

Vest4

0.013

MPC

0.092

ClinPred

0.0018

GERP RS

-0.53

Varity_R

0.087

gMVP

0.40

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over