Submissions for variant NM_025136.4(OPA3):c.241G>A (p.Ala81Thr)

gnomAD frequency: 0.00002  dbSNP: rs186796646

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000197168	SCV000252022	uncertain significance	not provided	2016-06-17	criteria provided, single submitter	clinical testing	p.Ala81Thr (GCA>ACA):c.241 G>A in exon 2 of the OPA3 gene (NM_025136.3) A variant of unknown significance identified in the OPA3 gene, A81T, has not been published as a mutation or a benign polymorphism to our knowledge. The amino acid change is non-conservative in that a non-polar Alanine residue is replaced by a polar Threonine residue. This change occurs at a highly conserved position in the OPA3 protein. In silico analyses are not consistent in their predictions of whether or not A81T is damaging to the OPA3 protein. Therefore, based on the currently available information it is unclear whether A81T would be a disease causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV002515419	SCV003033107	uncertain significance	3-Methylglutaconic aciduria type 3; Optic atrophy 3	2022-08-05	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 81 of the OPA3 protein (p.Ala81Thr). This variant is present in population databases (rs186796646, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with OPA3-related conditions. ClinVar contains an entry for this variant (Variation ID: 214927). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Clinical Genetics, Academic Medical Center	RCV000197168	SCV001923188	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000197168	SCV001971642	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001828027	SCV002088919	uncertain significance	3-Methylglutaconic aciduria type 3	2019-11-11	no assertion criteria provided	clinical testing