3-38754064-A-G

Variant names:

• chr3-38754064-A-G
• rs6599254
• NM_006514.4:c.1462-1552T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006514.4(SCN10A):​c.1462-1552T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,146 control chromosomes in the GnomAD database, including 38,264 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 0.69 (38264 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.1462-1552T>C		intron_variant	Intron 11 of 27	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.1462-1552T>C		intron_variant	Intron 11 of 27	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.1462-1552T>C		intron_variant	Intron 10 of 26			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.1489-1552T>C		intron_variant	Intron 11 of 27			ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105583 AN: 152028 Hom.: 38191 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.695 AC: 105722 AN: 152146 Hom.: 38264 Cov.: 32 AF XY: 0.693 AC XY: 51555 AN XY: 74386

African (AFR) AF: 0.906 AC: 37640 AN: 41536

American (AMR) AF: 0.669 AC: 10226 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3466

East Asian (EAS) AF: 0.859 AC: 4455 AN: 5184

South Asian (SAS) AF: 0.669 AC: 3221 AN: 4818

European-Finnish (FIN) AF: 0.530 AC: 5599 AN: 10568

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40434 AN: 67964

Other (OTH) AF: 0.648 AC: 1367 AN: 2110

Alfa AF: 0.644 Hom.: 44540

Bravo AF: 0.714

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.5
DANN	Benign	0.68
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6599254; hg19: chr3-38795555;