rs199474672

Positions:

• chrM-5537-A-AT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

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

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNW frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:3 O:1 Leigh-Syndrome
• Conservation: PhyloP100: 0.787

Genes affected

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

ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) 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; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-5537-A-AT is Pathogenic according to our data. Variant chrM-5537-A-AT is described in ClinVar as [Pathogenic]. Clinvar id is 9555.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNW	unassigned_transcript_4794	c.26_27insT	p.Lys9fs	frameshift_variant	1/1
ND2	unassigned_transcript_4793	c.*26_*27insT		downstream_gene_variant
TRNA	unassigned_transcript_4795	c.*49_*50insA		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

Leigh-Syndrome

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 01, 2003	- -

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Oct 23, 2020

- -

Mitochondrial encephalopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199474672; hg19: chrM-5538;