Genetic Variant SCN5A:c.*2145_*2146insGAGAAGAGAGTAGGAAAAAGGAGGG (chr3-38548175-T-TCCCTCCTTTTTCCTACTCTCTTCTC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000335.5(SCN5A):c.*2145_*2146insGAGAAGAGAGTAGGAAAAAGGAGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.99 ( 74187 hom., cov: 0)

Exomes 𝑓: 1.0 ( 2 hom. )

Consequence

SCN5A
NM_000335.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:7

Conservation

PhyloP100: 0.612

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 3-38548175-T-TCCCTCCTTTTTCCTACTCTCTTCTC is Benign according to our data. Variant chr3-38548175-T-TCCCTCCTTTTTCCTACTCTCTTCTC is described in ClinVar as [Likely_benign]. Clinvar id is 345061.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN5A	NM_001099404.2 link	c.2145_2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	Exon 28 of 28	ENST00000413689.6	NP_001092874.1	Q14524H9KVD2
SCN5A	NM_000335.5 link	c.2145_2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	Exon 28 of 28	ENST00000423572.7	NP_000326.2	Q14524-2Q86V90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689 link	c.2145_2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	Exon 28 of 28	5	NM_001099404.2	ENSP00000410257.1		H9KVD2
SCN5A	ENST00000423572 link	c.2145_2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	Exon 28 of 28	1	NM_000335.5	ENSP00000398266.2		Q14524-2

Frequencies

GnomAD3 genomes

AF:

0.988

AC:

150077

AN:

151932

Hom.:

74128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

0.986

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.979

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.982

Gnomad OTH

AF:

0.987

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

GnomAD4 genome

AF:

0.988

AC:

150195

AN:

152050

Hom.:

74187

Cov.:

AF XY:

0.988

AC XY:

73434

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

0.986

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.979

Gnomad4 NFE

AF:

0.982

Gnomad4 OTH

AF:

0.987

Alfa

AF:

0.977

Hom.:

2152

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Paroxysmal familial ventricular fibrillation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Progressive familial heart block

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated Cardiomyopathy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brugada syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital long QT syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sick sinus syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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