4-83264303-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001358921.2(COQ2):āc.1012A>Gā(p.Thr338Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,572 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 (ā ā ).
Frequency
Consequence
NM_001358921.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247672Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134374
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460356Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6AN XY: 726388
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1162A>G (p.T388A) alteration is located in exon 7 (coding exon 7) of the COQ2 gene. This alteration results from a A to G substitution at nucleotide position 1162, causing the threonine (T) at amino acid position 388 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 388 of the COQ2 protein (p.Thr388Ala). This variant is present in population databases (rs757878117, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with COQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1472809). 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 COQ2 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