M-7486-G-A

Position:

• chrM-7486-G-A

Variant summary

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

The ENST00000387416.2(MT-TS1):​n.29C>T variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TS1 ENST00000387416.2 non_coding_transcript_exon
• Scores: Mitotip Uncertain 13
• Clinical Significance: Uncertain significance no assertion criteria provided U:1 CPEO
• Conservation: PhyloP100: 9.63

Genes affected

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

TRNS1 (HGNC:):

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]

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

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
TRNS1	TRNS1.1	n.29C>T		non_coding_transcript_exon_variant	1/1
COX1	COX1.1			downstream_gene_variant			YP_003024028.1
TRND	TRND.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TS1	ENST00000387416.2	n.29C>T		non_coding_transcript_exon_variant	1/1
MT-CO1	ENST00000361624.2			downstream_gene_variant				ENSP00000354499	P1
MT-TD	ENST00000387419.1			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

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56433

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56433

Mitomap

CPEO

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Progressive external ophthalmoplegia Uncertain:1

Uncertain significance, no assertion criteria provided

research

Center for Neuroscience and Cell Biology, University of Coimbra, Portugal

Dec 22, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
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: rs1556423295; hg19: chrM-7487;