Variant: NC_012920.1(MT-ATP6):m.8783G>A

Version: 1.1
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CA414798058

692983 (ClinVar)

Gene: MT-ATP6 (HGNC:4508)

Condition: mitochondrial disease

Inheritance Mode: Mitochondrial inheritance

UUID: 3bb82672-99f3-4d9d-8909-d6b9559b3339

Approved on: 2024-12-09

Published on: 2025-05-19

HGVS expressions

NC_012920.1:m.8783G>A
J01415.2:m.8783G>A
ENST00000361899.2:c.257G>A

Uncertain Significance

• Met criteria codes: PP3

• Not Met criteria codes: PS3 PS2 PS4 PP1 PM2 PM6

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Criteria Specification: ClinGen Mitochondrial Disease Nuclear and Mitochondrial Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1_mtDNA

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The m.8783G>A (p.G86E) variant in MT-ATP6 has been reported in one individual with primary mitochondrial disease to date however clinical details are not provided (PMID: 32652755). There are no reports of large families with this variant segregating with disease. There are no reported de novo occurrences of this variant to our knowledge. This variant is present in population databases (0.002%; one homoplasmic occurrence in MITOMAP; one homoplasmic and six heteroplasmic occurrences in gnomAD v3.1.2; four homoplasmic and nine heteroplasmic occurrences in the Helix database). The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.59 (Min=0, Max=1; APOGEE2 score is 0.819), which predicts a damaging effect on gene function (PP3). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on December 9, 2024. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PP3.

Met criteria codes

• PP3: The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.59 (Min=0, Max=1; APOGEE2 score is 0.819), which predicts a damaging effect on gene function (PP3).

Not Met criteria codes

• PS3: There are no cybrids, single fiber studies, or other functional assays reported on this variant.
• PS2: There are no reported de novo occurrences of this variant to our knowledge.
• PS4: The m.8783G>A (p.G86E) variant in MT-ATP6 has been reported in one individual with primary mitochondrial disease to date however clinical details are not provided (PMID: 32652755).
• PP1: There are no reports of large families with this variant segregating with disease.
• PM2: This variant is present in population databases (0.002%; one homoplasmic occurrence in MITOMAP; one homoplasmic and six heteroplasmic occurrences in gnomAD v3.1.2; four homoplasmic and nine heteroplasmic occurrences in the Helix database).
• PM6: There are no reported de novo occurrences of this variant to our knowledge.