Variant: NC_012920.1(MT-ATP6):m.8704A>G

CA10581258

235260 (ClinVar)

Gene: N/A

Condition: mitochondrial disease

Inheritance Mode: Mitochondrial inheritance

UUID: 2e32eada-3289-4538-a299-9e19ca879902

Approved on: 2023-09-26

Published on: 2025-06-04

HGVS expressions

NC_012920.1:m.8704A>G
J01415.2:m.8704A>G
ENST00000361899.2:c.178A>G

Uncertain Significance

• Met criteria codes: BP4

• Not Met criteria codes: PS3 PS4 PM2

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.8704A>G (p.M60V) variant in MT-ATP6 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on September 26, 2023. There are no individuals or families with primary mitochondrial disease with this variant reported in the medical literature to our knowledge. This variant is present in population databases and is seen in individuals from several different haplogroups (MITOMAP: 0.039%, 24/61,883; gnomAD v3.1.2: 0.023%, 13/56,434 homoplasmic occurrences; Helix: 0.009%, 18/195,893 homoplasmic occurrences in addition to three heteroplasmic occurrences). The computational predictor APOGEE gives a consensus rating of neutral with a score of 0.37 (Min=0, Max=1), which predicts no effect on gene function (BP4). There are no cybrids, single fiber studies, or other functional assays reported for 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 September 26, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4.

Met criteria codes

• BP4: The computational predictor APOGEE gives a consensus rating of neutral with a score of 0.37 (Min=0, Max=1), which predicts no effect on gene function (BP4).

Not Met criteria codes

• PS3: There are no cybrids, single fiber studies, or other functional assays reported for this variant.
• PS4: There are no individuals or families with primary mitochondrial disease with this variant reported in the medical literature to our knowledge.
• PM2: This variant is present in population databases and is seen in individuals from several different haplogroups (MITOMAP: 0.039%, 24/61,883; gnomAD v3.1.2: 0.023%, 13/56,434 homoplasmic occurrences; Helix: 0.009%, 18/195,893 homoplasmic occurrences in addition to three heteroplasmic occurrences).