rs6793245

Variant names:

• chr3-38557546-G-A
• rs6793245
• NM_001099404.2:c.4246-262C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-38557546-G-A
• chr3-38557546-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000335.5(SCN5A):​c.4243-262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,012 control chromosomes in the GnomAD database, including 13,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (13449 hom., cov: 32)
• Consequence: SCN5A NM_000335.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

Genes affected

SCN5A (HGNC:10593): (sodium voltage-gated channel alpha subunit 5) The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene have been associated with long QT syndrome type 3 (LQT3), atrial fibrillation, cardiomyopathy, and Brugada syndrome 1, all autosomal dominant cardiac diseases. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 3-38557546-G-A is Benign according to our data. Variant chr3-38557546-G-A is described in ClinVar as [Benign]. Clinvar id is 680771.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN5A	NM_001099404.2	c.4246-262C>T		intron_variant	Intron 23 of 27	ENST00000413689.6	NP_001092874.1
SCN5A	NM_000335.5	c.4243-262C>T		intron_variant	Intron 23 of 27	ENST00000423572.7	NP_000326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689.6	c.4246-262C>T		intron_variant	Intron 23 of 27	5	NM_001099404.2	ENSP00000410257.1
SCN5A	ENST00000423572.7	c.4243-262C>T		intron_variant	Intron 23 of 27	1	NM_000335.5	ENSP00000398266.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60778 AN: 151894 Hom.: 13421 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.400 AC: 60852 AN: 152012 Hom.: 13449 Cov.: 32 AF XY: 0.401 AC XY: 29767 AN XY: 74310

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.391

Alfa AF: 0.338 Hom.: 15784

Bravo AF: 0.411

Asia WGS AF: 0.339 AC: 1182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.83

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: rs6793245; hg19: chr3-38599037;