rs6798015

Positions:

• chr3-38757345-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006514.4(SCN10A):​c.951-186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,094 control chromosomes in the GnomAD database, including 37,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (37968 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-38757345-C-T is Benign according to our data. Variant chr3-38757345-C-T is described in ClinVar as [Benign]. Clinvar id is 669276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.951-186G>A		intron_variant		ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.951-186G>A		intron_variant		1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.951-186G>A		intron_variant				ENSP00000495595.1
SCN10A	ENST00000655275.1	c.978-186G>A		intron_variant				ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105996 AN: 151976 Hom.: 37902 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.698 AC: 106127 AN: 152094 Hom.: 37968 Cov.: 32 AF XY: 0.695 AC XY: 51633 AN XY: 74330

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.654

Alfa AF: 0.638 Hom.: 41530

Bravo AF: 0.712

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.71

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: rs6798015; hg19: chr3-38798836;