rs6768664

chr3-38642975-C-Achr3-38642975-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.-53+6556G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,130 control chromosomes in the GnomAD database, including 24,619 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 0.57 (24619 hom., cov: 33)
• Consequence: SCN5A NM_001099404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN5A	NM_000335.5	c.-53+6556G>T		intron_variant		ENST00000423572.7
SCN5A	NM_001099404.2	c.-53+6556G>T		intron_variant		ENST00000413689.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN5A	ENST00000413689.6	c.-53+6556G>T		intron_variant		5	NM_001099404.2	P4
SCN5A	ENST00000423572.7	c.-53+6556G>T		intron_variant		1	NM_000335.5	A1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85948 AN: 152012 Hom.: 24578 Cov.: 33

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.566 AC: 86044 AN: 152130 Hom.: 24619 Cov.: 33 AF XY: 0.566 AC XY: 42078 AN XY: 74376

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.575

Alfa AF: 0.533 Hom.: 10766

Bravo AF: 0.581

Asia WGS AF: 0.579 AC: 2017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.021
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: rs6768664; hg19: chr3-38684466;