Variant: NC_012920.1(MT-ATP8):m.8553C>T

CA414796661

618720 (ClinVar)

Gene: MT-ATP8

Condition: mitochondrial disease

Inheritance Mode: Mitochondrial inheritance

UUID: bb4e86f8-3f2d-49f3-b92e-4c2fbde40d4e

Approved on: 2023-06-26

Published on: 2025-06-03

HGVS expressions

NC_012920.1:m.8553C>T
J01415.2:m.8553C>T
ENST00000361851.1:c.188C>T
ENST00000361899.2:c.27C>T

Uncertain Significance

• Met criteria codes: PP3

• Not Met criteria codes: PM2 PM6 PS3 PS4 PS2

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.8553C>T (p.F9F in MT-ATP6; p.S63L in MT-ATP8) was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on June 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: 0.023%, 14/61,883; gnomAD v3.1.2: 0.041%, 23/56,428 homoplasmic occurrences; Helix: 0.009%, 18/195,893 homoplasmic occurrences). The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.7 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). 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 June 26, 2023. 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 0.7 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3).

Not Met criteria codes

• PM2: This variant is present in population databases and is seen in individuals from several different haplogroups (MITOMAP: 0.023%, 14/61,883; gnomAD v3.1.2: 0.041%, 23/56,428 homoplasmic occurrences; Helix: 0.009%, 18/195,893 homoplasmic occurrences).
• PM6: There are no individuals or families with primary mitochondrial disease with this variant reported in the medical literature to our knowledge.
• 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.
• PS2: There are no individuals or families with primary mitochondrial disease with this variant reported in the medical literature to our knowledge.