rs763157740
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_005472.5(KCNE3):c.262C>T(p.Arg88Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88H) has been classified as Uncertain significance.
Frequency
Consequence
NM_005472.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE3 | NM_005472.5 | c.262C>T | p.Arg88Cys | missense_variant | 3/3 | ENST00000310128.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE3 | ENST00000310128.9 | c.262C>T | p.Arg88Cys | missense_variant | 3/3 | 1 | NM_005472.5 | P1 | |
KCNE3 | ENST00000525550.1 | c.262C>T | p.Arg88Cys | missense_variant | 2/2 | 1 | P1 | ||
ENST00000533008.1 | n.155-26875G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
KCNE3 | ENST00000532569.5 | c.262C>T | p.Arg88Cys | missense_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251324Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135872
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461868Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 727238
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
Brugada syndrome 6 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2020 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KCNE3-related disease. This variant is present in population databases (rs763157740, ExAC 0.002%). This sequence change replaces arginine with cysteine at codon 88 of the KCNE3 protein (p.Arg88Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 03, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2023 | The p.R88C variant (also known as c.262C>T), located in coding exon 1 of the KCNE3 gene, results from a C to T substitution at nucleotide position 262. The arginine at codon 88 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at