rs7433723

chr3-38743466-G-Achr3-38743466-G-T

Variant summary

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

The NM_006514.4(SCN10A):c.1868-937C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,094 control chromosomes in the GnomAD database, including 34,634 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 0.66 (34634 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4	c.1868-937C>T		intron_variant		ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN10A	ENST00000449082.3	c.1868-937C>T		intron_variant		1	NM_006514.4	P4
SCN10A	ENST00000643924.1	c.1868-937C>T		intron_variant				A1
SCN10A	ENST00000655275.1	c.1895-937C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100864 AN: 151976 Hom.: 34566 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.664 AC: 100998 AN: 152094 Hom.: 34634 Cov.: 32 AF XY: 0.661 AC XY: 49114 AN XY: 74338

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.625

Alfa AF: 0.637 Hom.: 5892

Bravo AF: 0.678

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.6
Dann	Benign	0.60

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: rs7433723; hg19: chr3-38784957;