dbSNP rs116353929: SCN10A:p.Asp1739Asp (chr3-38698003-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006514.4(SCN10A):c.5217C>T(p.Asp1739Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 1,614,122 control chromosomes in the GnomAD database, including 861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 44 hom., cov: 32)

Exomes 𝑓: 0.031 ( 817 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.285

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-38698003-G-A is Benign according to our data. Variant chr3-38698003-G-A is described in ClinVar as Benign. ClinVar VariationId is 240680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.285 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0225 (3428/152244) while in subpopulation NFE AF = 0.0329 (2237/68014). AF 95% confidence interval is 0.0318. There are 44 homozygotes in GnomAd4. There are 1635 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3428 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN10A	NM_006514.4	MANE Select	c.5217C>T	p.Asp1739Asp	synonymous	Exon 28 of 28	NP_006505.4
SCN10A	NM_001293306.2		c.5214C>T	p.Asp1738Asp	synonymous	Exon 27 of 27	NP_001280235.2
SCN10A	NM_001293307.2		c.4923C>T	p.Asp1641Asp	synonymous	Exon 26 of 26	NP_001280236.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN10A	ENST00000449082.3	TSL:1 MANE Select	c.5217C>T	p.Asp1739Asp	synonymous	Exon 28 of 28	ENSP00000390600.2
SCN10A	ENST00000643924.1		c.5214C>T	p.Asp1738Asp	synonymous	Exon 27 of 27	ENSP00000495595.1
SCN10A	ENST00000655275.1		c.5241C>T	p.Asp1747Asp	synonymous	Exon 28 of 28	ENSP00000499510.1

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3426

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0251

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0329

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.0263

AC:

6610

AN:

251198

AF XY:

0.0267

show subpopulations

Gnomad AFR exome

AF:

0.00547

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0251

Gnomad NFE exome

AF:

0.0316

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0315

AC:

46038

AN:

1461878

Hom.:

817

Cov.:

AF XY:

0.0316

AC XY:

22974

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00523

AC:

175

AN:

33480

American (AMR)

AF:

0.0309

AC:

1381

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

453

AN:

26136

East Asian (EAS)

AF:

0.000982

AC:

AN:

39698

South Asian (SAS)

AF:

0.0300

AC:

2584

AN:

86258

European-Finnish (FIN)

AF:

0.0228

AC:

1216

AN:

53420

Middle Eastern (MID)

AF:

0.00919

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0347

AC:

38547

AN:

1112000

Other (OTH)

AF:

0.0263

AC:

1590

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2896

5792

8688

11584

14480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1468

2936

4404

5872

7340

<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:

0.0225

AC:

3428

AN:

152244

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

1635

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00590

AC:

245

AN:

41546

American (AMR)

AF:

0.0233

AC:

357

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3468

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0291

AC:

140

AN:

4818

European-Finnish (FIN)

AF:

0.0251

AC:

266

AN:

10610

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0329

AC:

2237

AN:

68014

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

169

338

508

677

846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0291

Hom.:

Bravo

AF:

0.0225

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0325

EpiControl

AF:

0.0296

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Brugada syndrome (1)

Cardiovascular phenotype (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.013

(source)

DANN

Benign

0.40

PhyloP100

-0.28

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over