rs757284769
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018127.7(ELAC2):c.1645G>A(p.Ala549Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,613,850 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. A549V) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELAC2 | NM_018127.7 | c.1645G>A | p.Ala549Thr | missense_variant | 17/24 | ENST00000338034.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELAC2 | ENST00000338034.9 | c.1645G>A | p.Ala549Thr | missense_variant | 17/24 | 1 | NM_018127.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251044Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135756
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461670Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727158
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2021 | The c.1645G>A (p.A549T) alteration is located in exon 17 (coding exon 17) of the ELAC2 gene. This alteration results from a G to A substitution at nucleotide position 1645, causing the alanine (A) at amino acid position 549 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Combined oxidative phosphorylation defect type 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 549 of the ELAC2 protein (p.Ala549Thr). This variant is present in population databases (rs757284769, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ELAC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 474561). 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 not expected to disrupt ELAC2 protein function with a negative predictive value of 80%. 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