rs7641844

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 260000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38760760-A-G is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.884-13T>C		intron_variant		ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.884-13T>C		intron_variant		1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.884-13T>C		intron_variant				ENSP00000495595.1
SCN10A	ENST00000655275.1	c.914-16T>C		intron_variant				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

GnomAD3 exomes AF: 0.327 AC: 81671 AN: 249692 Hom.: 14838 AF XY: 0.326 AC XY: 43999 AN XY: 134960

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 SAS exome AF: 0.352

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

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.359

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.308

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

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.303

Alfa AF: 0.288 Hom.: 14006

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

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Brugada syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Episodic pain syndrome, familial, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.86

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

LitVar

Other links and lift over

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