Variant 3-38548867-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000423572.7(SCN5A):c.*1453_*1454insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,570 control chromosomes in the GnomAD database, including 6,170 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 6166 hom., cov: 29)

Exomes 𝑓: 0.15 ( 4 hom. )

Consequence

SCN5A
ENST00000423572.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0610

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 -16 ACMG points.

BP6

Variant 3-38548867-C-CT is Benign according to our data. Variant chr3-38548867-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 345077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN5A	NM_000335.5 linkuse as main transcript	c.1453_1454insA		3_prime_UTR_variant	28/28	ENST00000423572.7	NP_000326.2
SCN5A	NM_001099404.2 linkuse as main transcript	c.1453_1454insA		3_prime_UTR_variant	28/28	ENST00000413689.6	NP_001092874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689.6 linkuse as main transcript	c.1453_1454insA		3_prime_UTR_variant	28/28	5	NM_001099404.2	ENSP00000410257	P4
SCN5A	ENST00000423572.7 linkuse as main transcript	c.1453_1454insA		3_prime_UTR_variant	28/28	1	NM_000335.5	ENSP00000398266	A1	Q14524-2

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34606

AN:

152018

Hom.:

6128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.0910

Gnomad OTH

AF:

0.217

GnomAD4 exome

AF:

0.147

AC:

AN:

434

Hom.:

Cov.:

AF XY:

0.134

AC XY:

AN XY:

262

show subpopulations

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.228

AC:

34692

AN:

152136

Hom.:

6166

Cov.:

AF XY:

0.229

AC XY:

17054

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.0910

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.165

Hom.:

447

Bravo

AF:

0.244

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Progressive familial heart block

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Paroxysmal familial ventricular fibrillation

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Dilated Cardiomyopathy, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Brugada syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Congenital long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Sick sinus syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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