chr22-41499741-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP2PP3BP4
The NM_001098.3(ACO2):c.52C>T(p.Arg18Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000098 in 1,612,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R18Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001098.3 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 |
---|---|---|---|---|---|---|---|
ACO2 | NM_001098.3 | c.52C>T | p.Arg18Trp | missense_variant | 2/18 | ENST00000216254.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACO2 | ENST00000216254.9 | c.52C>T | p.Arg18Trp | missense_variant | 2/18 | 1 | NM_001098.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000184 AC: 46AN: 250326Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135340
GnomAD4 exome AF: 0.0000897 AC: 131AN: 1460400Hom.: 0 Cov.: 31 AF XY: 0.0000840 AC XY: 61AN XY: 726542
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 18 of the ACO2 protein (p.Arg18Trp). This variant is present in population databases (rs201569120, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with ACO2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACO2 protein function with a positive predictive value of 95%. 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