rs77173739
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001354663.2(OPA1):c.-47T>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000105 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001354663.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247902Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134486
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461600Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727124
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:5
Reported as a likely benign variant in a study identifying OPA1 variants (PMID: 33884488); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33884488) -
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This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 109 of the OPA1 protein (p.Val109Ala). This variant is present in population databases (rs77173739, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with OPA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 586198). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt OPA1 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at