chr3-38763097-C-T

Variant names:

• chr3-38763097-C-T
• rs6599257
• NM_006514.4:c.691+408G>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.691+408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,096 control chromosomes in the GnomAD database, including 42,514 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 0.74 (42514 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.691+408G>A		intron_variant	Intron 6 of 27	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.691+408G>A		intron_variant	Intron 6 of 27	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.691+408G>A		intron_variant	Intron 5 of 26			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.691+408G>A		intron_variant	Intron 6 of 27			ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112871 AN: 151978 Hom.: 42459 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.743 AC: 112987 AN: 152096 Hom.: 42514 Cov.: 32 AF XY: 0.741 AC XY: 55080 AN XY: 74352

African (AFR) AF: 0.864 AC: 35851 AN: 41482

American (AMR) AF: 0.717 AC: 10960 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3468

East Asian (EAS) AF: 0.865 AC: 4480 AN: 5178

South Asian (SAS) AF: 0.718 AC: 3454 AN: 4810

European-Finnish (FIN) AF: 0.617 AC: 6522 AN: 10568

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46906 AN: 67982

Other (OTH) AF: 0.701 AC: 1480 AN: 2112

Alfa AF: 0.712 Hom.: 130516

Bravo AF: 0.757

Asia WGS AF: 0.789 AC: 2744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.025
DANN	Benign	0.37
PhyloP100		-1.9
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: rs6599257; hg19: chr3-38804588;