rs374389286
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PVS1_StrongBP6BS2
The NM_012282.4(KCNE5):c.55G>T(p.Glu19*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,208,817 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 152 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_012282.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNE5 | NM_012282.4 | c.55G>T | p.Glu19* | stop_gained | 1/1 | ENST00000372101.3 | NP_036414.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNE5 | ENST00000372101.3 | c.55G>T | p.Glu19* | stop_gained | 1/1 | 6 | NM_012282.4 | ENSP00000361173.2 | ||
ACSL4 | ENST00000439581.1 | n.387-645G>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 26AN: 113070Hom.: 0 Cov.: 25 AF XY: 0.000256 AC XY: 9AN XY: 35220
GnomAD3 exomes AF: 0.000194 AC: 33AN: 170214Hom.: 0 AF XY: 0.000200 AC XY: 12AN XY: 60046
GnomAD4 exome AF: 0.000401 AC: 439AN: 1095747Hom.: 0 Cov.: 31 AF XY: 0.000395 AC XY: 143AN XY: 361613
GnomAD4 genome AF: 0.000230 AC: 26AN: 113070Hom.: 0 Cov.: 25 AF XY: 0.000256 AC XY: 9AN XY: 35220
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | KCNE5: BS2 - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 25, 2023 | This sequence change creates a premature translational stop signal (p.Glu19*) in the KCNE5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 124 amino acid(s) of the KCNE5 protein. This variant is present in population databases (rs374389286, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with KCNE5-related conditions. ClinVar contains an entry for this variant (Variation ID: 581565). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
KCNE5-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 20, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at