rs121434454

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000000000(TRND):​c.9A>G​(p.Leu3Leu) variant causes a synonymous change. Variant has been reported in ClinVar as Uncertain significance (★★★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRND ENST00000000000 synonymous
• Scores: Mitotip Uncertain 13
• Clinical Significance: Pathogenic no assertion criteria provided P:1 Mitochondrial-myopathy
• Conservation: PhyloP100: 7.18
• Publications: 1 publications found

Genes affected

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

MT-CO2 (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]

MT-CO1 (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]

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

TRNS1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.

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
MT-TD	ENST00000387419.1	n.9A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-CO2	ENST00000361739.1	c.-60A>G		upstream_gene_variant		6		ENSP00000354876.1
MT-CO1	ENST00000361624.2	c.*81A>G		downstream_gene_variant		6		ENSP00000354499.2
MT-TS1	ENST00000387416.2	n.-12T>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Alfa AF: 0.00 Hom.: 0

Mitomap

Disease(s): Mitochondrial-myopathy

Status: Reported

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Pathogenic	0.60
PhyloP100		7.2
Mutation Taster		=65/35	polymorphism

Other links and lift over

dbSNP: rs121434454; hg19: chrM-7527;