rs200868190
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001099404.2(SCN5A):c.1734C>T(p.Pro578=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,874 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P578P) has been classified as Likely benign.
Frequency
Consequence
NM_001099404.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.1734C>T | p.Pro578= | synonymous_variant | 12/28 | ENST00000413689.6 | |
SCN5A | NM_000335.5 | c.1734C>T | p.Pro578= | synonymous_variant | 12/28 | ENST00000423572.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.1734C>T | p.Pro578= | synonymous_variant | 12/28 | 5 | NM_001099404.2 | P4 | |
SCN5A | ENST00000423572.7 | c.1734C>T | p.Pro578= | synonymous_variant | 12/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152192Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248706Hom.: 1 AF XY: 0.0000222 AC XY: 3AN XY: 134896
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461564Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727066
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152310Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 29, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 03, 2020 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 10, 2015 | p.Pro578Pro in exon 12 of SCN5A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 6/9770 African ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs200868190). - |
Cardiac arrhythmia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 07, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 08, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at