Variant chr3-38557115-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001099404.2(SCN5A):c.4299+116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 870,902 control chromosomes in the GnomAD database, including 13,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4011 hom., cov: 33)

Exomes 𝑓: 0.16 ( 9640 hom. )

Consequence

SCN5A
NM_001099404.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.496

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-38557115-C-T is Benign according to our data. Variant chr3-38557115-C-T is described in ClinVar as [Benign]. Clinvar id is 672393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38557115-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN5A	NM_000335.5 linkuse as main transcript	c.4296+116G>A		intron_variant		ENST00000423572.7
SCN5A	NM_001099404.2 linkuse as main transcript	c.4299+116G>A		intron_variant		ENST00000413689.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN5A	ENST00000413689.6 linkuse as main transcript	c.4299+116G>A		intron_variant		5	NM_001099404.2	P4
SCN5A	ENST00000423572.7 linkuse as main transcript	c.4296+116G>A		intron_variant		1	NM_000335.5	A1	Q14524-2

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31575

AN:

151968

Hom.:

3997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0950

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.159

AC:

114001

AN:

718816

Hom.:

9640

AF XY:

0.157

AC XY:

58753

AN XY:

373562

show subpopulations

Gnomad4 AFR exome

AF:

0.352

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.208

AC:

31627

AN:

152086

Hom.:

4011

Cov.:

AF XY:

0.206

AC XY:

15338

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.355

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.0954

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.108

Hom.:

261

Bravo

AF:

0.216

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over