3-38697226-G-A

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.*123C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,470,942 control chromosomes in the GnomAD database, including 147,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (14628 hom., cov: 32)
  • Exomes 𝑓: 0.44 (132506 hom.)
• Consequence: SCN10A NM_006514.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.649

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=-0.73).
• BP6: Variant 3-38697226-G-A is Benign according to our data. Variant chr3-38697226-G-A is described in ClinVar as [Benign]. Clinvar id is 1259657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4	c.*123C>T		3_prime_UTR_variant	28/28	ENST00000449082.3
SCN10A	XM_005265371.4	c.*123C>T		3_prime_UTR_variant	27/27
SCN10A	XM_011533993.3	c.*123C>T		3_prime_UTR_variant	27/27
SCN10A	XM_011533994.3	c.*123C>T		3_prime_UTR_variant	26/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN10A	ENST00000449082.3	c.*123C>T		3_prime_UTR_variant	28/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1	c.*123C>T		3_prime_UTR_variant	28/28

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66303 AN: 151894 Hom.: 14636 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.444 AC: 585843 AN: 1318930 Hom.: 132506 Cov.: 21 AF XY: 0.445 AC XY: 287556 AN XY: 646802

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.433

GnomAD4 genome AF: 0.436 AC: 66308 AN: 152012 Hom.: 14628 Cov.: 32 AF XY: 0.432 AC XY: 32106 AN XY: 74296

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.452

Alfa AF: 0.451 Hom.: 22803

Bravo AF: 0.430

Asia WGS AF: 0.297 AC: 1036 AN: 3476

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	10
Dann	Benign	0.77

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: rs6599240; hg19: chr3-38738717; COSMIC: COSV71862339; COSMIC: COSV71862339;