rs118192104

Variant names:

• chrM-8361-G-A
• rs118192104
• unassigned_transcript_4803:c.67G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000000000(TRNK):​c.67G>A​(p.Val23Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNK ENST00000000000 missense
• Scores: Mitotip Uncertain 15
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1 MERRF
• Conservation: PhyloP100: 0.0280
• Publications: 2 publications found

Genes affected

TRNK (HGNC:7489): (mitochondrially encoded tRNA lysine)

MT-ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

MT-ATP8 (HGNC:7415): (mitochondrially encoded ATP synthase 8) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in multiple sclerosis and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

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-CO2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• MELAS syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-8361-G-A is Pathogenic according to our data. Variant chrM-8361-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 9585.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNK	unassigned_transcript_4803	c.67G>A	p.Val23Met	missense_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.-166G>A		upstream_gene_variant
ATP8	unassigned_transcript_4804	c.-5G>A		upstream_gene_variant
COX2	unassigned_transcript_4802	c.*92G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TK	ENST00000387421.1	n.67G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-ATP6	ENST00000361899.2	c.-166G>A		upstream_gene_variant		6		ENSP00000354632.2
MT-ATP8	ENST00000361851.1	c.-5G>A		upstream_gene_variant		6		ENSP00000355265.1
MT-CO2	ENST00000361739.1	c.*92G>A		downstream_gene_variant		6		ENSP00000354876.1

Frequencies

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

Mitomap

Disease(s): MERRF

Status: Reported

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

MERRF syndrome Pathogenic:1 Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Pathogenic variants identified in approximately 10% of persons w/MERRF -

Dec 01, 2003

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	15
Hmtvar	Pathogenic	0.55
PhyloP100		0.028
Mutation Taster		=99/1	polymorphism

Other links and lift over

dbSNP: rs118192104; hg19: chrM-8362;