chr11-74457301-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005472.5(KCNE3):c.263G>A(p.Arg88His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R88C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005472.5 missense
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 |
---|---|---|---|---|---|---|---|
KCNE3 | NM_005472.5 | c.263G>A | p.Arg88His | missense_variant | 3/3 | ENST00000310128.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE3 | ENST00000310128.9 | c.263G>A | p.Arg88His | missense_variant | 3/3 | 1 | NM_005472.5 | P1 | |
KCNE3 | ENST00000525550.1 | c.263G>A | p.Arg88His | missense_variant | 2/2 | 1 | P1 | ||
ENST00000533008.1 | n.155-26876C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
KCNE3 | ENST00000532569.5 | c.263G>A | p.Arg88His | missense_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251318Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135872
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461860Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 727240
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 27, 2024 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2024 | The p.R88H variant (also known as c.263G>A), located in coding exon 1 of the KCNE3 gene, results from a G to A substitution at nucleotide position 263. The arginine at codon 88 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Brugada syndrome 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 88 of the KCNE3 protein (p.Arg88His). This variant is present in population databases (rs17221833, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with KCNE3-related conditions. ClinVar contains an entry for this variant (Variation ID: 190801). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at