rs17215437
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005472.5(KCNE3):āc.248G>Cā(p.Arg83Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R83H) has been classified as Likely benign.
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.248G>C | p.Arg83Pro | missense_variant | 3/3 | ENST00000310128.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE3 | ENST00000310128.9 | c.248G>C | p.Arg83Pro | missense_variant | 3/3 | 1 | NM_005472.5 | P1 | |
KCNE3 | ENST00000525550.1 | c.248G>C | p.Arg83Pro | missense_variant | 2/2 | 1 | P1 | ||
ENST00000533008.1 | n.155-26861C>G | intron_variant, non_coding_transcript_variant | 3 | ||||||
KCNE3 | ENST00000532569.5 | c.248G>C | p.Arg83Pro | missense_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461844Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727232
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2024 | The p.R83P variant (also known as c.248G>C), located in coding exon 1 of the KCNE3 gene, results from a G to C substitution at nucleotide position 248. The arginine at codon 83 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. 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. - |
Brugada syndrome 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 11, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1406921). This variant has not been reported in the literature in individuals affected with KCNE3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 83 of the KCNE3 protein (p.Arg83Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at