3-38564241-G-C

Position:

• chr3-38564241-G-C

Variant summary

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

The NM_000335.5(SCN5A):​c.3838-1704C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 151,952 control chromosomes in the GnomAD database, including 43,908 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 0.76 (43908 hom., cov: 30)
• Consequence: SCN5A NM_000335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN5A	NM_001099404.2	c.3841-1704C>G		intron_variant		ENST00000413689.6	NP_001092874.1
SCN5A	NM_000335.5	c.3838-1704C>G		intron_variant		ENST00000423572.7	NP_000326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689.6	c.3841-1704C>G		intron_variant		5	NM_001099404.2	ENSP00000410257.1
SCN5A	ENST00000423572.7	c.3838-1704C>G		intron_variant		1	NM_000335.5	ENSP00000398266.2

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115259 AN: 151834 Hom.: 43867 Cov.: 30

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.759 AC: 115358 AN: 151952 Hom.: 43908 Cov.: 30 AF XY: 0.763 AC XY: 56695 AN XY: 74270

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.735

Alfa AF: 0.735 Hom.: 5127

Bravo AF: 0.755

Asia WGS AF: 0.829 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.67

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: rs7374138; hg19: chr3-38605732;