Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NC_012920.1:m.9152T>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10581404

235698 (ClinVar)

Gene: N/A

Condition: mitochondrial disease

Inheritance Mode: Mitochondrial inheritance

Link to MONDO

UUID: 29009a8a-0d25-48f1-9087-f35640d7f94d

Approved on: 2023-06-26

Published on: 2024-07-24

HGVS expressions

NC_012920.1:m.9152T>C

J01415.2:m.9152T>C

ENST00000361899.2:c.626T>C

Uncertain Significance

BP4

PM2 PM6 PS4 PS3 PS2

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The m.9152T>C (p.I209T) variant in MT-ATP6 has been reported in one case to date, in an individual with autism, fatigue, reflux, and constipation (PMID: 30763462) who had the variant present at 23% in blood. The proband's healthy mother had the variant present at 10% in blood. There are no reported de novo occurrences to our knowledge. The computational predictor APOGEE gives a consensus rating of neutral with a score of 0.47 (Min=0, Max=1), which predicts no damaging effect on gene function (BP4). 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 June 26, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4.

BP4

The computational predictor APOGEE gives a consensus rating of neutral with a score of 0.47 (Min=0, Max=1), which predicts no damaging effect on gene function (BP4).

PM2

This variant is present in population databases (Mitomap's 17/59,389 sequences: AF=0.029%; Helix's 50/195,983 sequences: AF=0.026%; and gnomAD v3.1.2: AF=0.012% as this is homoplasmic in 7 individuals and heteroplasmic in 5 individuals). Given the frequency of this variant, it does not meet PM2 criterion.

PM6

There are no reported de novo occurrences of this variant to our knowledge.

PS4

There are no individuals with this variant reported in the medical literature to our knowledge.

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.

Curation History

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