rs6800541

Variant names:

• chr3-38733341-C-T
• rs6800541
• NM_006514.4:c.2281-4440G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 59 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 -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 rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.2281-4440G>A		intron_variant	Intron 15 of 27	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.2281-4440G>A		intron_variant	Intron 15 of 27	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.2281-4440G>A		intron_variant	Intron 14 of 26			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.2308-4440G>A		intron_variant	Intron 15 of 27			ENSP00000499510.1

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

African (AFR) AF: 0.906 AC: 37589 AN: 41492

American (AMR) AF: 0.670 AC: 10221 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2089 AN: 3468

East Asian (EAS) AF: 0.860 AC: 4449 AN: 5176

South Asian (SAS) AF: 0.665 AC: 3193 AN: 4802

European-Finnish (FIN) AF: 0.537 AC: 5629 AN: 10482

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40636 AN: 67986

Other (OTH) AF: 0.650 AC: 1368 AN: 2106

Alfa AF: 0.630 Hom.: 128633

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6800541; hg19: chr3-38774832;