rs9833086

chr3-38568980-G-A

Variant summary

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

The NM_001099404.2(SCN5A):c.3667-2398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,906 control chromosomes in the GnomAD database, including 34,465 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 0.67 (34465 hom., cov: 32)
• Consequence: SCN5A NM_001099404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN5A	NM_000335.5	c.3664-2398C>T		intron_variant		ENST00000423572.7
SCN5A	NM_001099404.2	c.3667-2398C>T		intron_variant		ENST00000413689.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN5A	ENST00000413689.6	c.3667-2398C>T		intron_variant		5	NM_001099404.2	P4
SCN5A	ENST00000423572.7	c.3664-2398C>T		intron_variant		1	NM_000335.5	A1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101536 AN: 151788 Hom.: 34436 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.669 AC: 101621 AN: 151906 Hom.: 34465 Cov.: 32 AF XY: 0.675 AC XY: 50159 AN XY: 74256

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.676

Alfa AF: 0.705 Hom.: 42008

Bravo AF: 0.653

Asia WGS AF: 0.729 AC: 2513 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.58
Dann	Benign	0.53

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: rs9833086; hg19: chr3-38610471;