rs7433723

Variant names:

• chr3-38743466-G-A
• rs7433723
• NM_006514.4:c.1868-937C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-38743466-G-A
• chr3-38743466-G-T

Variant summary

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

The NM_006514.4(SCN10A):​c.1868-937C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,094 control chromosomes in the GnomAD database, including 34,634 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 0.66 (34634 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN10A	NM_006514.4	MANE Select	c.1868-937C>T		intron	N/A	NP_006505.4
	SCN10A	NM_001293306.2		c.1868-937C>T		intron	N/A	NP_001280235.2
	SCN10A	NM_001293307.2		c.1574-937C>T		intron	N/A	NP_001280236.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN10A	ENST00000449082.3	TSL:1 MANE Select	c.1868-937C>T		intron	N/A	ENSP00000390600.2
	SCN10A	ENST00000643924.1		c.1868-937C>T		intron	N/A	ENSP00000495595.1
	SCN10A	ENST00000655275.1		c.1895-937C>T		intron	N/A	ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100864 AN: 151976 Hom.: 34566 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.664 AC: 100998 AN: 152094 Hom.: 34634 Cov.: 32 AF XY: 0.661 AC XY: 49114 AN XY: 74338

African (AFR) AF: 0.847 AC: 35159 AN: 41494

American (AMR) AF: 0.600 AC: 9177 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4147 AN: 5170

South Asian (SAS) AF: 0.627 AC: 3019 AN: 4816

European-Finnish (FIN) AF: 0.523 AC: 5517 AN: 10556

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39903 AN: 67988

Other (OTH) AF: 0.625 AC: 1317 AN: 2108

Alfa AF: 0.700 Hom.: 11059

Bravo AF: 0.678

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.60
PhyloP100		1.3
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: rs7433723; hg19: chr3-38784957;