M-4275-G-A

Variant names:

• chrM-4275-G-A
• unassigned_transcript_4790:c.13G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNI missense
• Scores: Mitotip Uncertain 12
• Clinical Significance: Pathogenic criteria provided, single submitter P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 6.39

Genes affected

TRNI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-4275-G-A is Pathogenic according to our data. Variant chrM-4275-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3255383.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNI	unassigned_transcript_4790	c.13G>A	p.Asp5Asn	missense_variant	Exon 1 of 1
ND2	unassigned_transcript_4793	c.-195G>A		upstream_gene_variant
TRNM	unassigned_transcript_4792	c.-127G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap

No disease associated.

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Progressive external ophthalmoplegia Pathogenic:1

Mar 01, 2024

Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: in vitro;research

PS2+PS3+PM2(ACMG Guidelines, 2015) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	12
Hmtvar	Benign	0.050

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrM-4276;