rs6800541

chr3-38733341-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006514.4(SCN10A):c.2281-4440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 151,974 control chromosomes in the GnomAD database, including 38,356 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (38356 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4	c.2281-4440G>A		intron_variant		ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN10A	ENST00000449082.3	c.2281-4440G>A		intron_variant		1	NM_006514.4	P4
SCN10A	ENST00000643924.1	c.2281-4440G>A		intron_variant				A1
SCN10A	ENST00000655275.1	c.2308-4440G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105715 AN: 151856 Hom.: 38283 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.697 AC: 105854 AN: 151974 Hom.: 38356 Cov.: 32 AF XY: 0.695 AC XY: 51589 AN XY: 74240

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.650

Alfa AF: 0.613 Hom.: 63722

Bravo AF: 0.715

Asia WGS AF: 0.775 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.056
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6800541; hg19: chr3-38774832;