rs6599250

Variant names:

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.1868-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,609,664 control chromosomes in the GnomAD database, including 316,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38358 hom., cov: 32)

Exomes 𝑓: 0.61 ( 277776 hom. )

Consequence

SCN10A
NM_006514.4 intron

Scores

Splicing: ADA: 0.00006857

Clinical Significance

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

Conservation

PhyloP100: -0.669

Publications

22 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 (BayesDel_noAF=-0.79).

BP6

Variant 3-38742538-T-C is Benign according to our data. Variant chr3-38742538-T-C is described in ClinVar as Benign. ClinVar VariationId is 259993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4 link	c.1868-9A>G		intron_variant	Intron 13 of 27	ENST00000449082.3	NP_006505.4	Q9Y5Y9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN10A	ENST00000449082.3 link	c.1868-9A>G	intron_variant	Intron 13 of 27	1	NM_006514.4	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1 link	c.1868-9A>G	intron_variant	Intron 12 of 26			ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1 link	c.1895-9A>G	intron_variant	Intron 13 of 27			ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105735

AN:

151962

Hom.:

38285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.647

GnomAD2 exomes

AF:

0.649

AC:

161550

AN:

248812

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.911

Gnomad AMR exome

AF:

0.686

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.860

Gnomad FIN exome

AF:

0.540

Gnomad NFE exome

AF:

0.596

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.614

AC:

894283

AN:

1457584

Hom.:

277776

Cov.:

AF XY:

0.613

AC XY:

444436

AN XY:

725452

show subpopulations

African (AFR)

AF:

0.916

AC:

30636

AN:

33436

American (AMR)

AF:

0.684

AC:

30579

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

15685

AN:

26112

East Asian (EAS)

AF:

0.858

AC:

34024

AN:

39674

South Asian (SAS)

AF:

0.637

AC:

54914

AN:

86186

European-Finnish (FIN)

AF:

0.542

AC:

28835

AN:

53200

Middle Eastern (MID)

AF:

0.535

AC:

3078

AN:

5748

European-Non Finnish (NFE)

AF:

0.594

AC:

658567

AN:

1108246

Other (OTH)

AF:

0.630

AC:

37965

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

18794

37587

56381

75174

93968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18134

36268

54402

72536

90670

<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:

0.696

AC:

105874

AN:

152080

Hom.:

38358

Cov.:

AF XY:

0.694

AC XY:

51596

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.907

AC:

37640

AN:

41518

American (AMR)

AF:

0.670

AC:

10243

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2098

AN:

3462

East Asian (EAS)

AF:

0.860

AC:

4444

AN:

5168

South Asian (SAS)

AF:

0.661

AC:

3176

AN:

4808

European-Finnish (FIN)

AF:

0.534

AC:

5641

AN:

10558

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.597

AC:

40581

AN:

67952

Other (OTH)

AF:

0.649

AC:

1372

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1539

3079

4618

6158

7697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.644

Hom.:

53933

Bravo

AF:

0.715

Asia WGS

AF:

0.769

AC:

2675

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 04, 2023

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

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

- -

Sep 06, 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. -

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

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.9

(source)

DANN

Benign

0.71

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000069

dbscSNV1_RF

Benign

0.010

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

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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