19-45529131-C-CAGCT
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_001017989.3(OPA3):c.464_467dupAGCT(p.Gln157AlafsTer77) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001017989.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
3-Methylglutaconic aciduria type 3;C1833809:Optic atrophy 3 Uncertain:1
This sequence change results in a frameshift in the OPA3 gene (p.Gln157Alafs*77). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the OPA3 protein and extend the protein by 52 additional amino acid residues. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with OPA3-related conditions. This variant is not present in population databases (gnomAD no frequency). The OPA3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001017989.2, which corresponds to position c.*24379_*24382dup in NM_025136.3, the primary transcript listed in the Methods. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at