chr3-38548175-T-TCCCTCCTTTTTCCTACTCTCTTCTC

Position:

• chr3-38548175-T-TCCCTCCTTTTTCCTACTCTCTTCTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:7
• Conservation: PhyloP100: 0.612

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 -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/exons	MANE	Protein	UniProt
SCN5A	NM_001099404.2	c.*2145_*2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	28/28	ENST00000413689.6	NP_001092874.1
SCN5A	NM_000335.5	c.*2145_*2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	28/28	ENST00000423572.7	NP_000326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689	c.*2145_*2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	28/28	5	NM_001099404.2	ENSP00000410257.1
SCN5A	ENST00000423572	c.*2145_*2146insGAGAAGAGAGTAGGAAAAAGGAGGG		3_prime_UTR_variant	28/28	1	NM_000335.5	ENSP00000398266.2

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150077 AN: 151932 Hom.: 74128 Cov.: 0

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: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.988 AC: 150195 AN: 152050 Hom.: 74187 Cov.: 0 AF XY: 0.988 AC XY: 73434 AN XY: 74308

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

Submissions by phenotype

Paroxysmal familial ventricular fibrillation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Progressive familial heart block 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

- -

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs45592631; hg19: chr3-38589666;