chr17-13015806-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_018127.7(ELAC2):c.394G>A(p.Gly132Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000129 in 1,613,858 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. G132A) has been classified as Uncertain significance.
Frequency
Consequence
NM_018127.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELAC2 | NM_018127.7 | c.394G>A | p.Gly132Arg | missense_variant | 4/24 | ENST00000338034.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELAC2 | ENST00000338034.9 | c.394G>A | p.Gly132Arg | missense_variant | 4/24 | 1 | NM_018127.7 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251170Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135832
GnomAD4 exome AF: 0.000137 AC: 200AN: 1461724Hom.: 0 Cov.: 30 AF XY: 0.000139 AC XY: 101AN XY: 727172
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74310
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 17 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Phosphorus, Inc. | Aug 01, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 25, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 132 of the ELAC2 protein (p.Gly132Arg). This variant is present in population databases (rs374005835, gnomAD 0.009%). This missense change has been observed in individual(s) with complex hyperkinetic syndrome and acanthocytosis (PMID: 30217939). ClinVar contains an entry for this variant (Variation ID: 488161). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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