rs375008004
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_012282.4(KCNE5):āc.305A>Cā(p.Glu102Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,203,630 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E102K) has been classified as Uncertain significance.
Frequency
Consequence
NM_012282.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE5 | NM_012282.4 | c.305A>C | p.Glu102Ala | missense_variant | 1/1 | ENST00000372101.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE5 | ENST00000372101.3 | c.305A>C | p.Glu102Ala | missense_variant | 1/1 | NM_012282.4 | P1 | ||
ACSL4 | ENST00000439581.1 | n.387-395A>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000177 AC: 2AN: 112887Hom.: 0 Cov.: 25 AF XY: 0.0000285 AC XY: 1AN XY: 35149
GnomAD4 exome AF: 0.0000156 AC: 17AN: 1090743Hom.: 0 Cov.: 31 AF XY: 0.0000112 AC XY: 4AN XY: 358205
GnomAD4 genome AF: 0.0000177 AC: 2AN: 112887Hom.: 0 Cov.: 25 AF XY: 0.0000285 AC XY: 1AN XY: 35149
ClinVar
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 240861). This variant has not been reported in the literature in individuals affected with KCNE5-related conditions. This variant is present in population databases (rs375008004, gnomAD 0.02%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 102 of the KCNE5 protein (p.Glu102Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at