Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • The variant label for this record ("m.9379G>A") does not appear to be in HGVS format
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: MT-CO3 CSPEC Genes: [] * Message MONDOs: MONDO:0044970 CSPEC MONDO: []
  • No CSPEC computed assertion could be determined for this classification!

Variant: m.9379G>A

CA120603

9657 (ClinVar)

Gene: MT-CO3
Condition: mitochondrial disease
Inheritance Mode: Mitochondrial inheritance
Link to MONDO
UUID: ab23d578-3d7b-41d1-92da-206f7268dc7f
Approved on: 2024-01-22
Published on: 2025-03-19

HGVS expressions

NC_012920.1:m.9379G>A
J01415.2:m.9379G>A
ENST00000362079.2:c.173G>A

Uncertain Significance

Met criteria codes 2
PVS1_Strong PM2_Supporting
Not Met criteria codes 1
PS4

Evidence Links 0

Expert Panel

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.9379G>A (p.W58Ter) variant in MT-CO3 has been reported in one individual with primary mitochondrial disease. This individual had childhood onset mitochondrial myopathy and lactic acidosis and harbored the variant at 93% heteroplasmy in muscle; however the variant was not detected in the proband's blood or hair. The variant was also undetectable in blood and hair from the healthy mother and blood from the healthy sister (PMID: 12414820). This variant introduces a premature termination codon in exon 58 out of 261, and is expected to remove 78% of the protein (PVS1_strong). This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). There are no in silico predictors for this type of variant in mitochondrial DNA. 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 January 22, 2024. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PVS1_strong, PM2_supporting.
Met criteria codes
PVS1_Strong
This variant introduces a premature termination codon in exon 58 out of 261, and is expected to remove 78% of the protein (PVS1_Strong).
PM2_Supporting
This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting).
Not Met criteria codes
PS4
The m.9379G>A (p.W58Ter) variant in MT-CO3 has been reported in one individual with features of primary mitochondrial disease. This individual had childhood onset mitochondrial myopathy and lactic acidosis and harbored the variant at 93% heteroplasmy in muscle; however the variant was not detected in the proband's blood or hair (PMID 12414820). This does not meet criteria for PS4_supporting which requires at least two unrelated affected individuals.
Curation History
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