M-7453-G-A

Position:

• chrM-7453-G-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2 PP5_Very_Strong

The ENST00000387416.2(MT-TS1):​n.62C>T variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TS1 ENST00000387416.2 non_coding_transcript_exon
• Scores: Mitotip Uncertain 15
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2 Fatal-neonatal-lactic-acidosis-/-Neonatal-lactic-acidosis+-exercise-intolerance+-mild-ID
• Conservation: PhyloP100: 4.86

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-7453-G-A is Pathogenic according to our data. Variant chrM-7453-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 869395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNS1	TRNS1.1	n.62C>T		non_coding_transcript_exon_variant	1/1
COX1	COX1.1			downstream_gene_variant			YP_003024028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TS1	ENST00000387416.2	n.62C>T		non_coding_transcript_exon_variant	1/1
MT-CO1	ENST00000361624.2			downstream_gene_variant				ENSP00000354499	P1

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: 56427

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56427

Mitomap

Fatal-neonatal-lactic-acidosis-/-Neonatal-lactic-acidosis+-exercise-intolerance+-mild-ID

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

neonatal lactic acidosis Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Kids Research, The Children's Hospital at Westmead

-

- -

Mitochondrial complex IV deficiency, nuclear type 1 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	15
Hmtvar	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2068703521; hg19: chrM-7454; COSMIC: COSV62293979;