M-5545-C-T

Position:

• chrM-5545-C-T

Variant summary

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

The ENST00000387382.1(MT-TW):​n.34C>T variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Uncertain significance (★★★).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-TW ENST00000387382.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 13
• Clinical Significance: Pathogenic no assertion criteria provided P:1 HCM-severe-multisystem-disorder
• Conservation: PhyloP100: 4.72

Genes affected

MT-TW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNW (HGNC:):

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]

MT-TA (HGNC:7475): (mitochondrially encoded tRNA alanine)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Mitotip and hmtvar scores support pathogenic criterium.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNW	TRNW.1	n.34C>T		non_coding_transcript_exon_variant	1/1
TRNA	TRNA.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TW	ENST00000387382.1	n.34C>T		non_coding_transcript_exon_variant	1/1
MT-ND2	ENST00000361453.3			downstream_gene_variant				P1
MT-TA	ENST00000387392.1			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap

HCM-severe-multisystem-disorder

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Encephalocardiomyopathy, mitochondrial Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 15, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	13
Hmtvar	Pathogenic	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs387906418; hg19: chrM-5546;