NM_006514.4:c.1284G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006514.4(SCN10A):c.1284G>A(p.Glu428Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,192 control chromosomes in the GnomAD database, including 47,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3662 hom., cov: 31)

Exomes 𝑓: 0.24 ( 44038 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.490

Publications

17 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 -19 ACMG points.

BP4

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

BP6

Variant 3-38756680-C-T is Benign according to our data. Variant chr3-38756680-C-T is described in ClinVar as Benign. ClinVar VariationId is 259991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4 link	c.1284G>A	p.Glu428Glu	synonymous_variant	Exon 10 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.1284G>A	p.Glu428Glu	synonymous_variant	Exon 10 of 28	1	NM_006514.4	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1 link	c.1284G>A	p.Glu428Glu	synonymous_variant	Exon 9 of 27			ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1 link	c.1311G>A	p.Glu437Glu	synonymous_variant	Exon 10 of 28			ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31127

AN:

151958

Hom.:

3662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.202

GnomAD2 exomes

AF:

0.231

AC:

57831

AN:

250870

AF XY:

0.236

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.240

AC:

350749

AN:

1460116

Hom.:

44038

Cov.:

AF XY:

0.241

AC XY:

174949

AN XY:

726506

show subpopulations

African (AFR)

AF:

0.101

AC:

3375

AN:

33466

American (AMR)

AF:

0.111

AC:

4960

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

8554

AN:

26122

East Asian (EAS)

AF:

0.427

AC:

16934

AN:

39690

South Asian (SAS)

AF:

0.234

AC:

20171

AN:

86228

European-Finnish (FIN)

AF:

0.259

AC:

13711

AN:

52984

Middle Eastern (MID)

AF:

0.217

AC:

1230

AN:

5672

European-Non Finnish (NFE)

AF:

0.241

AC:

267712

AN:

1110874

Other (OTH)

AF:

0.234

AC:

14102

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

14573

29147

43720

58294

72867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9100

18200

27300

36400

45500

<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:

0.205

AC:

31130

AN:

152076

Hom.:

3662

Cov.:

AF XY:

0.206

AC XY:

15315

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.104

AC:

4327

AN:

41514

American (AMR)

AF:

0.138

AC:

2116

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1173

AN:

3472

East Asian (EAS)

AF:

0.402

AC:

2072

AN:

5160

South Asian (SAS)

AF:

0.242

AC:

1162

AN:

4804

European-Finnish (FIN)

AF:

0.258

AC:

2723

AN:

10554

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16778

AN:

67964

Other (OTH)

AF:

0.200

AC:

422

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1213

2426

3639

4852

6065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.223

Hom.:

3042

Bravo

AF:

0.192

Asia WGS

AF:

0.270

AC:

940

AN:

3478

EpiCase

AF:

0.238

EpiControl

AF:

0.239

ClinVar

Significance: 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

- -

Sep 22, 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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 17, 2017

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

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: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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Brugada syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

BayesDel_noAF

Benign

-0.39

CADD

Benign

3.2

(source)

DANN

Benign

0.48

PhyloP100

-0.49

Mutation Taster

=100/0

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

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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