3-38736063-T-G

Variant names:

• chr3-38736063-T-G
• rs10428132
• NM_006514.4:c.2280+3452A>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.2280+3452A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,092 control chromosomes in the GnomAD database, including 35,393 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 0.67 (35393 hom., cov: 33)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 52 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.2280+3452A>C		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.2280+3452A>C		intron_variant	Intron 15 of 27	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.2280+3452A>C		intron_variant	Intron 14 of 26			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.2307+3452A>C		intron_variant	Intron 15 of 27			ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101860 AN: 151974 Hom.: 35324 Cov.: 33

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.671 AC: 101994 AN: 152092 Hom.: 35393 Cov.: 33 AF XY: 0.667 AC XY: 49602 AN XY: 74346

African (AFR) AF: 0.861 AC: 35774 AN: 41536

American (AMR) AF: 0.605 AC: 9239 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2087 AN: 3466

East Asian (EAS) AF: 0.802 AC: 4142 AN: 5164

South Asian (SAS) AF: 0.635 AC: 3061 AN: 4818

European-Finnish (FIN) AF: 0.529 AC: 5585 AN: 10554

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40104 AN: 67960

Other (OTH) AF: 0.630 AC: 1328 AN: 2108

Alfa AF: 0.618 Hom.: 103561

Bravo AF: 0.685

Asia WGS AF: 0.731 AC: 2543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.9
DANN	Benign	0.68
PhyloP100		-0.057
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: rs10428132; hg19: chr3-38777554;