Genetic Variant TRNY:p.Pro22Ser (chrM-5828-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Mitomap GenBank:

𝑓 0.0 ( AC: 0 )

Consequence

TRNY
missense, splice_region

Scores

Mitotip

Uncertain

Clinical Significance

Pathogenic criteria provided, single submitter P:1

No linked disesase in Mitomap

Conservation

PhyloP100: 0.564

Variant links:

Genes affected

TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

TRNY links:

COX1 (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]

COX1 links:

TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

TRNN links:

TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNA links:

TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

TRNC links:

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNW links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very low frequency in mitomap database: 0.0

PP5

Variant M-5828-G-A is Pathogenic according to our data. Variant chrM-5828-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3255385.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank
TRNY	unassigned_transcript_4798	c.64C>T	p.Pro22Ser	missense_variant, splice_region_variant	Exon 1 of 1
COX1	unassigned_transcript_4799	c.-76G>A		upstream_gene_variant
TRNN	unassigned_transcript_4796	c.-99C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome

Cov.:

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

Mitomap GenBank

AF:

0.0

AC:

Gnomad homoplasmic

AF:

0.0

AC:

AN:

56431

Gnomad heteroplasmic

AF:

0.000018

AC:

AN:

56431

Mitomap

No disease associated.

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Progressive external ophthalmoplegia

Pathogenic:1

Mar 01, 2024

Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: in vitro;research

PS2+PS3+PM2(ACMG Guidelines, 2015) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mitotip

Uncertain

Hmtvar

Benign

0.050

Splicing

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

Publications

No publications associated with this variant yet.