3-38723999-C-T

Variant names:

• chr3-38723999-C-T
• rs7430477
• NM_006514.4:c.3229-446G>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.3229-446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,974 control chromosomes in the GnomAD database, including 14,693 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 0.44 (14693 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 5 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=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.464 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.3229-446G>A		intron	N/A	NP_006505.4
	SCN10A	NM_001293306.2		c.3226-446G>A		intron	N/A	NP_001280235.2
	SCN10A	NM_001293307.2		c.2935-446G>A		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.3229-446G>A		intron	N/A	ENSP00000390600.2
	SCN10A	ENST00000643924.1		c.3226-446G>A		intron	N/A	ENSP00000495595.1
	SCN10A	ENST00000655275.1		c.3253-446G>A		intron	N/A	ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66421 AN: 151856 Hom.: 14693 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.437 AC: 66445 AN: 151974 Hom.: 14693 Cov.: 32 AF XY: 0.434 AC XY: 32265 AN XY: 74270

African (AFR) AF: 0.423 AC: 17525 AN: 41412

American (AMR) AF: 0.343 AC: 5237 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1782 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2127 AN: 5164

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4810

European-Finnish (FIN) AF: 0.431 AC: 4543 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31831 AN: 67962

Other (OTH) AF: 0.417 AC: 879 AN: 2108

Alfa AF: 0.459 Hom.: 30329

Bravo AF: 0.430

Asia WGS AF: 0.378 AC: 1316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.74
PhyloP100		2.0
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: rs7430477; hg19: chr3-38765490;