M-12192-G-T

Variant names:

• chrM-12192-G-T
• rs3134560
• unassigned_transcript_4812:c.55G>T

Variant summary

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

The ENST00000000000(TRNH):​c.55G>T​(p.Asp19Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: TRNH ENST00000000000 missense
• Scores: Mitotip Benign 2.7
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -4.60
• Publications: 0 publications found

Genes affected

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) 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; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• PM2: Very low frequency in mitomap database: 0.0

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387441.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TH	ENST00000387441.1	TSL:6	n.55G>T		non_coding_transcript_exon	Exon 1 of 1
	MT-ND5	ENST00000361567.2	TSL:6	c.-145G>T		upstream_gene	N/A	ENSP00000354813.2
	MT-ND4	ENST00000361381.2	TSL:6	c.*55G>T		downstream_gene	N/A	ENSP00000354961.2

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.7
Hmtvar	Benign	0.0
PhyloP100		-4.6

Other links and lift over

dbSNP: rs3134560; hg19: chrM-12193;