rs199474666
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The ENST00000386347.1(MT-TL1):n.45A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Mitomap GenBank:
Absent
Consequence
MT-TL1
ENST00000386347.1 non_coding_transcript_exon
ENST00000386347.1 non_coding_transcript_exon
Scores
Mitotip
Pathogenic
Clinical Significance
Neuropsychiatric-syndrome-+-cataract
Conservation
PhyloP100: 0.987
Genes affected
MT-TL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]
MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]
MT-RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
No frequency data in Mitomap. Probably very rare.
PP3
?
Mitotip and hmtvar scores support pathogenic criterium.
PP5
?
Variant M-3274-A-G is Pathogenic according to our data. Variant chrM-3274-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 9598.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRNL1 | TRNL1.1 use as main transcript | n.45A>G | non_coding_transcript_exon_variant | 1/1 | |||
RNR2 | RNR2.1 use as main transcript | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-TL1 | ENST00000386347.1 | n.45A>G | non_coding_transcript_exon_variant | 1/1 | |||||
MT-ND1 | ENST00000361390.2 | upstream_gene_variant | P1 | ||||||
MT-RNR2 | ENST00000387347.2 | downstream_gene_variant |
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap
Neuropsychiatric-syndrome-+-cataract
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:2Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Neuropsychiatric disorder and early-onset cataract Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 27, 2001 | - - |
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Jul 12, 2019 | The NC_012920.1:m.3274A>G variant in MT-TL1 gene is interpreted to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PS3, PM7, PM8, PM9 - |
MERRF syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Aug 23, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Mitotip
Pathogenic
Hmtvar
Pathogenic
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at