rs199474672

Variant names:

• chrM-5537-A-AT
• rs199474672
• unassigned_transcript_4794:c.26_27insT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The ENST00000000000(TRNW):​c.26_27insT​(p.Lys9fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Mitomap GenBank: Absent
• Consequence: TRNW ENST00000000000 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:3 O:1 Leigh-Syndrome
• Conservation: PhyloP100: 0.787
• Publications: 1 publications found

Genes affected

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

MT-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]

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

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

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

TRNC Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 9555.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNW	unassigned_transcript_4794	c.26_27insT	p.Lys9fs	frameshift_variant	Exon 1 of 1
ND2	unassigned_transcript_4793	c.*26_*27insT		downstream_gene_variant
TRNN	unassigned_transcript_4796	c.*119_*120insA		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.*26_*27insT		downstream_gene_variant		6		ENSP00000355046.4

Frequencies

Mitomap GenBank The variant is not present, suggesting it is rare .

Mitomap

Disease(s): Leigh-Syndrome

Status: Cfrm-[LP]

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Pathogenic:1 Other:1

Apr 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

not provided Pathogenic:1

Oct 23, 2020

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mitochondrial encephalopathy Pathogenic:1

Apr 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79

Other links and lift over

dbSNP: rs199474672; hg19: chrM-5538;