rs9311195

Positions:

• chr3-38639727-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099404.2(SCN5A):​c.-52-6368G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,148 control chromosomes in the GnomAD database, including 2,180 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 0.17 (2180 hom., cov: 32)
• Consequence: SCN5A NM_001099404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN5A	NM_000335.5	c.-52-6368G>C		intron_variant		ENST00000423572.7
SCN5A	NM_001099404.2	c.-52-6368G>C		intron_variant		ENST00000413689.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN5A	ENST00000413689.6	c.-52-6368G>C		intron_variant		5	NM_001099404.2	P4
SCN5A	ENST00000423572.7	c.-52-6368G>C		intron_variant		1	NM_000335.5	A1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25691 AN: 152030 Hom.: 2179 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.169 AC: 25703 AN: 152148 Hom.: 2180 Cov.: 32 AF XY: 0.167 AC XY: 12443 AN XY: 74386

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.176

Alfa AF: 0.172 Hom.: 306

Bravo AF: 0.172

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.9
DANN	Benign	0.78

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: rs9311195; hg19: chr3-38681218;