chr3-38587421-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000335.5(SCN5A):c.2415G>A(p.Ser805Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
SCN5A
NM_000335.5 synonymous
NM_000335.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.91
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 3-38587421-C-T is Benign according to our data. Variant chr3-38587421-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 413940.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SCN5A | ENST00000413689.6 | c.2415G>A | p.Ser805Ser | synonymous_variant | 15/28 | 5 | NM_001099404.2 | ENSP00000410257.1 | ||
| SCN5A | ENST00000423572.7 | c.2415G>A | p.Ser805Ser | synonymous_variant | 15/28 | 1 | NM_000335.5 | ENSP00000398266.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248240Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134648
GnomAD3 exomes
AF:
AC:
8
AN:
248240
Hom.:
AF XY:
AC XY:
5
AN XY:
134648
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461138Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726792
GnomAD4 exome
AF:
AC:
22
AN:
1461138
Hom.:
Cov.:
31
AF XY:
AC XY:
12
AN XY:
726792
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2021 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 05, 2023 | - - |
Cardiovascular phenotype Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 02, 2023 | The c.2415G>A variant (also known as p.S805S), located in coding exon 14 of the SCN5A gene, results from a G to A substitution at nucleotide position 2415. This nucleotide substitution does not change the serine at codon 805. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at