3-38643344-C-G

Position:

• chr3-38643344-C-G

Variant summary

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

The ENST00000423572.7(SCN5A):​c.-53+6187G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,216 control chromosomes in the GnomAD database, including 2,890 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 0.18 (2890 hom., cov: 33)
• Consequence: SCN5A ENST00000423572.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN5A	NM_000335.5	c.-53+6187G>C		intron_variant		ENST00000423572.7	NP_000326.2
SCN5A	NM_001099404.2	c.-53+6187G>C		intron_variant		ENST00000413689.6	NP_001092874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689.6	c.-53+6187G>C		intron_variant		5	NM_001099404.2	ENSP00000410257	P4
SCN5A	ENST00000423572.7	c.-53+6187G>C		intron_variant		1	NM_000335.5	ENSP00000398266	A1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26705 AN: 152098 Hom.: 2886 Cov.: 33

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.175 AC: 26713 AN: 152216 Hom.: 2890 Cov.: 33 AF XY: 0.179 AC XY: 13330 AN XY: 74420

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0951 Hom.: 134

Bravo AF: 0.173

Asia WGS AF: 0.381 AC: 1324 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	6.9
DANN	Benign	0.72

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: rs7427574; hg19: chr3-38684835;