rs121434454

Variant names:

• chrM-7526-A-G
• rs121434454
• unassigned_transcript_4801:c.9A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRND synonymous
• Scores: Mitotip Uncertain 13
• Clinical Significance: Pathogenic no assertion criteria provided P:1 Mitochondrial-myopathy
• Conservation: PhyloP100: 7.18

Genes affected

TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

COX2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

COX1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-7526-A-G is Pathogenic according to our data. Variant chrM-7526-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 9619.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRND	unassigned_transcript_4801	c.9A>G	p.Leu3Leu	synonymous_variant	Exon 1 of 1
COX2	unassigned_transcript_4802	c.-60A>G		upstream_gene_variant
TRNS1	unassigned_transcript_4800	c.-12T>C		upstream_gene_variant
COX1	unassigned_transcript_4799	c.*81A>G		downstream_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

Mitochondrial-myopathy

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial myopathy, isolated Pathogenic:1

Aug 30, 2005

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Pathogenic	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs121434454; hg19: chrM-7527;