3-38565865-A-G

Position:

• chr3-38565865-A-G

Variant summary

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

The NM_000335.5(SCN5A):​c.3837+544T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,916 control chromosomes in the GnomAD database, including 17,946 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 0.46 (17946 hom., cov: 32)
• Consequence: SCN5A NM_000335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833

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]

SCN5A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN5A	NM_001099404.2	c.3840+544T>C		intron_variant		ENST00000413689.6	NP_001092874.1
SCN5A	NM_000335.5	c.3837+544T>C		intron_variant		ENST00000423572.7	NP_000326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689.6	c.3840+544T>C		intron_variant		5	NM_001099404.2	ENSP00000410257.1
SCN5A	ENST00000423572.7	c.3837+544T>C		intron_variant		1	NM_000335.5	ENSP00000398266.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70029 AN: 151798 Hom.: 17946 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.461 AC: 70069 AN: 151916 Hom.: 17946 Cov.: 32 AF XY: 0.466 AC XY: 34607 AN XY: 74232

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.498

Alfa AF: 0.475 Hom.: 2226

Bravo AF: 0.447

Asia WGS AF: 0.655 AC: 2276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.73

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: rs7372251; hg19: chr3-38607356;