3-38725824-T-C

Position:

• chr3-38725824-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000449082.3(SCN10A):​c.3088-510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,200 control chromosomes in the GnomAD database, including 35,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.67 (35019 hom., cov: 33)
• Consequence: SCN10A ENST00000449082.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.576

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=-0.47).
• BP6: Variant 3-38725824-T-C is Benign according to our data. Variant chr3-38725824-T-C is described in ClinVar as [Benign]. Clinvar id is 1165939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.3088-510A>G		intron_variant		ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.3088-510A>G		intron_variant		1	NM_006514.4	ENSP00000390600	P4
SCN10A	ENST00000643924.1	c.3088-513A>G		intron_variant				ENSP00000495595	A1
SCN10A	ENST00000655275.1	c.3115-513A>G		intron_variant				ENSP00000499510

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101624 AN: 152082 Hom.: 34951 Cov.: 33

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.669 AC: 101757 AN: 152200 Hom.: 35019 Cov.: 33 AF XY: 0.666 AC XY: 49537 AN XY: 74404

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.629

Alfa AF: 0.602 Hom.: 30755

Bravo AF: 0.682

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 27, 2020

This variant is associated with the following publications: (PMID: 24642470, 22706305, 21076409, 29448912) -

Brugada syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.82

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: rs6801957; hg19: chr3-38767315;