NM_001099404.2:c.1441C>T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_001099404.2(SCN5A):c.1441C>T(p.Arg481Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,613,928 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001099404.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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SCN5A | NM_001099404.2 | c.1441C>T | p.Arg481Trp | missense_variant | Exon 11 of 28 | ENST00000413689.6 | NP_001092874.1 | |
SCN5A | NM_000335.5 | c.1441C>T | p.Arg481Trp | missense_variant | Exon 11 of 28 | ENST00000423572.7 | NP_000326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.1441C>T | p.Arg481Trp | missense_variant | Exon 11 of 28 | 5 | NM_001099404.2 | ENSP00000410257.1 | ||
SCN5A | ENST00000423572.7 | c.1441C>T | p.Arg481Trp | missense_variant | Exon 11 of 28 | 1 | NM_000335.5 | ENSP00000398266.2 |
Frequencies
GnomAD3 genomes AF: 0.00340 AC: 517AN: 152158Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.000867 AC: 216AN: 249156Hom.: 2 AF XY: 0.000747 AC XY: 101AN XY: 135160
GnomAD4 exome AF: 0.000398 AC: 582AN: 1461652Hom.: 5 Cov.: 31 AF XY: 0.000366 AC XY: 266AN XY: 727108
GnomAD4 genome AF: 0.00342 AC: 521AN: 152276Hom.: 4 Cov.: 32 AF XY: 0.00357 AC XY: 266AN XY: 74462
ClinVar
Submissions by phenotype
not specified Benign:5
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Arg481Trp in exon 11 of SCN5A: This variant is not expected to have clinical sig nificance because it has been identified in 0.9% (29/3250) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs144511230). Arg481Trp in exon 11 of SCN5A ( rs144511230; allele frequency = 0.9%, 29/3250) ** -
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not provided Benign:4Other:1
This variant is associated with the following publications: (PMID: 29874177, 15992732) -
This variant has been reported in the following publications (PMID:19841300;PMID:20129283). -
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SCN5A: BS1, BS2 -
Cardiac arrhythmia Benign:2
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Brugada syndrome 1 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Ventricular fibrillation, paroxysmal familial, type 1 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Progressive familial heart block, type 1A Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Brugada syndrome Benign:1
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Brugada syndrome;C1859062:Long QT syndrome 3 Benign:1
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Dilated cardiomyopathy 1E Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Sick sinus syndrome 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Long QT syndrome 3 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Cardiovascular phenotype Benign:1
This alteration is classified as 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. -
Long QT syndrome 3;C4551804:Brugada syndrome 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at