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3-38548867-C-CT

Variant summary

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

The NM_001099404.2(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
NM_001099404.2 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]

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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 UniProt
SCN5ANM_000335.5 linkuse as main transcriptc.*1453_*1454insA 3_prime_UTR_variant 28/28 ENST00000423572.7
SCN5ANM_001099404.2 linkuse as main transcriptc.*1453_*1454insA 3_prime_UTR_variant 28/28 ENST00000413689.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCN5AENST00000413689.6 linkuse as main transcriptc.*1453_*1454insA 3_prime_UTR_variant 28/285 NM_001099404.2 P4
SCN5AENST00000423572.7 linkuse as main transcriptc.*1453_*1454insA 3_prime_UTR_variant 28/281 NM_000335.5 A1Q14524-2

Frequencies

GnomAD3 genomes
AF:
0.228
AC:
34606
AN:
152018
Hom.:
6128
Cov.:
29
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:
64
AN:
434
Hom.:
4
Cov.:
0
AF XY:
0.134
AC XY:
35
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.:
29
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 submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Paroxysmal familial ventricular fibrillation Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 14, 2021- -
Congenital long QT syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Sick sinus syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 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.

Other links and lift over

dbSNP: rs397763929; hg19: chr3-38590358; API