rs7641844

Variant names:

• chr3-38760760-A-G
• rs7641844
• NM_006514.4:c.884-13T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-38760760-A-G
• chr3-38760760-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006514.4(SCN10A):​c.884-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,605,174 control chromosomes in the GnomAD database, including 74,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7964 hom., cov: 32)
  • Exomes 𝑓: 0.29 (66828 hom.)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.17
• Publications: 11 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 3-38760760-A-G is Benign according to our data. Variant chr3-38760760-A-G is described in ClinVar as Benign. ClinVar VariationId is 260000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.884-13T>C		intron_variant	Intron 7 of 27	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.884-13T>C		intron_variant	Intron 7 of 27	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.884-13T>C		intron_variant	Intron 6 of 26			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.914-16T>C		intron_variant	Intron 7 of 27			ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47846 AN: 151970 Hom.: 7948 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.327 AC: 81671 AN: 249692 AF XY: 0.326

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.293 AC: 425567 AN: 1453086 Hom.: 66828 Cov.: 30 AF XY: 0.295 AC XY: 213118 AN XY: 723482

African (AFR) AF: 0.355 AC: 11810 AN: 33278

American (AMR) AF: 0.296 AC: 13243 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 9590 AN: 26074

East Asian (EAS) AF: 0.693 AC: 27476 AN: 39632

South Asian (SAS) AF: 0.359 AC: 30860 AN: 86064

European-Finnish (FIN) AF: 0.270 AC: 14410 AN: 53272

Middle Eastern (MID) AF: 0.287 AC: 1650 AN: 5748

European-Non Finnish (NFE) AF: 0.270 AC: 298013 AN: 1104244

Other (OTH) AF: 0.308 AC: 18515 AN: 60078

GnomAD4 genome AF: 0.315 AC: 47915 AN: 152088 Hom.: 7964 Cov.: 32 AF XY: 0.318 AC XY: 23667 AN XY: 74338

African (AFR) AF: 0.338 AC: 13998 AN: 41474

American (AMR) AF: 0.298 AC: 4551 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1295 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3554 AN: 5168

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4808

European-Finnish (FIN) AF: 0.268 AC: 2831 AN: 10582

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18847 AN: 67976

Other (OTH) AF: 0.303 AC: 641 AN: 2114

Alfa AF: 0.291 Hom.: 22991

Bravo AF: 0.319

Asia WGS AF: 0.492 AC: 1712 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

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 21, 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

- -

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

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		1.2
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs7641844; hg19: chr3-38802251; COSMIC: COSV71861141;