3-38697302-C-T

Variant names:

• chr3-38697302-C-T
• rs116283332
• NM_006514.4:c.*47G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006514.4(SCN10A):​c.*47G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,594,394 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (6 hom.)
• Consequence: SCN10A NM_006514.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.215
• Publications: 0 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=-0.67).
• BP6: Variant 3-38697302-C-T is Benign according to our data. Variant chr3-38697302-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1187276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00599 (912/152256) while in subpopulation AFR AF = 0.0206 (855/41532). AF 95% confidence interval is 0.0194. There are 8 homozygotes in GnomAd4. There are 429 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 912 AD,Unknown gene.

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.*47G>A		3_prime_UTR	Exon 28 of 28	NP_006505.4	Q9Y5Y9
	SCN10A	NM_001293306.2		c.*47G>A		downstream_gene	N/A	NP_001280235.2	Q9Y5Y9
	SCN10A	NM_001293307.2		c.*47G>A		downstream_gene	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.*47G>A		3_prime_UTR	Exon 28 of 28	ENSP00000390600.2	Q9Y5Y9
	SCN10A	ENST00000655275.1		c.*47G>A		3_prime_UTR	Exon 28 of 28	ENSP00000499510.1	A0A590UJM0
	SCN10A	ENST00000643924.1		c.*47G>A		downstream_gene	N/A	ENSP00000495595.1	A0A2R8Y6J6

Frequencies

GnomAD3 genomes AF: 0.00598 AC: 910 AN: 152138 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00168 AC: 400 AN: 238462 AF XY: 0.00125

Gnomad AFR exome AF: 0.0215

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000371

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.000599 AC: 864 AN: 1442138 Hom.: 6 Cov.: 32 AF XY: 0.000501 AC XY: 358 AN XY: 714538

African (AFR) AF: 0.0212 AC: 700 AN: 33022

American (AMR) AF: 0.00155 AC: 68 AN: 43810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39458

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52228

Middle Eastern (MID) AF: 0.000741 AC: 4 AN: 5400

European-Non Finnish (NFE) AF: 0.0000200 AC: 22 AN: 1100892

Other (OTH) AF: 0.00116 AC: 69 AN: 59498

GnomAD4 genome AF: 0.00599 AC: 912 AN: 152256 Hom.: 8 Cov.: 32 AF XY: 0.00576 AC XY: 429 AN XY: 74448

African (AFR) AF: 0.0206 AC: 855 AN: 41532

American (AMR) AF: 0.00288 AC: 44 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.0105 Hom.: 5

Bravo AF: 0.00724

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.67
CADD	Benign	7.1
DANN	Benign	0.76
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs116283332; hg19: chr3-38738793;