M-7554-G-A

Position:

• chrM-7554-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000387419.1(MT-TD):​n.37G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TD ENST00000387419.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 16
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 Myopathy+ataxia+nystagmus+migraines+lactic-acidosis
• Conservation: PhyloP100: 0.627

Genes affected

MT-TD (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

TRND (HGNC:):

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-TS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP3: Mitotip and hmtvar scores support pathogenic criterium.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRND	TRND.1	n.37G>A		non_coding_transcript_exon_variant	1/1
COX2	COX2.1			upstream_gene_variant			YP_003024029.1
TRNS1	TRNS1.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TD	ENST00000387419.1	n.37G>A		non_coding_transcript_exon_variant	1/1
MT-CO2	ENST00000361739.1			upstream_gene_variant				ENSP00000354876	P1
MT-TS1	ENST00000387416.2			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0 AC: 0

Alfa AF: 0.000112 Hom.: 0

Mitomap

Myopathy+ataxia+nystagmus+migraines+lactic-acidosis

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	16
Hmtvar	Pathogenic	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603221009; hg19: chrM-7555;