chr3-38757345-C-T

Variant names:

• chr3-38757345-C-T
• rs6798015
• NM_006514.4:c.951-186G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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):

• episodic pain syndrome, familial, 2

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• sodium channelopathy-related small fiber neuropathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN10A	NM_006514.4	MANE Select	c.951-186G>A		intron	N/A	NP_006505.4	Q9Y5Y9
	SCN10A	NM_001293306.2		c.951-186G>A		intron	N/A	NP_001280235.2	Q9Y5Y9
	SCN10A	NM_001293307.2		c.951-186G>A		intron	N/A	NP_001280236.2	Q9Y5Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN10A	ENST00000449082.3	TSL:1 MANE Select	c.951-186G>A		intron	N/A	ENSP00000390600.2	Q9Y5Y9
	SCN10A	ENST00000643924.1		c.951-186G>A		intron	N/A	ENSP00000495595.1	A0A2R8Y6J6
	SCN10A	ENST00000655275.1		c.978-186G>A		intron	N/A	ENSP00000499510.1	A0A590UJM0

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

African (AFR) AF: 0.867 AC: 36011 AN: 41530

American (AMR) AF: 0.632 AC: 9649 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2243 AN: 3468

East Asian (EAS) AF: 0.797 AC: 4117 AN: 5168

South Asian (SAS) AF: 0.684 AC: 3290 AN: 4812

European-Finnish (FIN) AF: 0.550 AC: 5807 AN: 10550

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42825 AN: 67972

Other (OTH) AF: 0.654 AC: 1379 AN: 2110

Alfa AF: 0.657 Hom.: 105724

Bravo AF: 0.712

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.71
PhyloP100		-0.27
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: rs6798015; hg19: chr3-38798836;