3-38548867-C-CT
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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
NM_001099404.2 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0610
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 |
---|---|---|---|---|---|---|---|
SCN5A | NM_000335.5 | c.*1453_*1454insA | 3_prime_UTR_variant | 28/28 | ENST00000423572.7 | ||
SCN5A | NM_001099404.2 | c.*1453_*1454insA | 3_prime_UTR_variant | 28/28 | ENST00000413689.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.*1453_*1454insA | 3_prime_UTR_variant | 28/28 | 5 | NM_001099404.2 | P4 | ||
SCN5A | ENST00000423572.7 | c.*1453_*1454insA | 3_prime_UTR_variant | 28/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.228 AC: 34606AN: 152018Hom.: 6128 Cov.: 29
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GnomAD4 exome AF: 0.147 AC: 64AN: 434Hom.: 4 Cov.: 0 AF XY: 0.134 AC XY: 35AN XY: 262
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GnomAD4 genome ? AF: 0.228 AC: 34692AN: 152136Hom.: 6166 Cov.: 29 AF XY: 0.229 AC XY: 17054AN XY: 74364
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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
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at