rs199474662
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PP5_Very_Strong
The ENST00000386347.1(MT-TL1):n.22A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Mitomap GenBank:
𝑓 0.0 ( AC: 0 )
Consequence
MT-TL1
ENST00000386347.1 non_coding_transcript_exon
ENST00000386347.1 non_coding_transcript_exon
Scores
Mitotip
Uncertain
Clinical Significance
MM-/-MELAS-with-chorea-ballism
Conservation
PhyloP100: 0.908
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-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 Pathogenic. Variant got 10 ACMG points.
PM2
?
Very low frequency in mitomap database: 0.0
PP5
?
Variant M-3251-A-G is Pathogenic according to our data. Variant chrM-3251-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 9595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRNL1 | TRNL1.1 use as main transcript | n.22A>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.22A>G | non_coding_transcript_exon_variant | 1/1 | |||||
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 GenBank
AF:
AC:
0
Mitomap
MM-/-MELAS-with-chorea-ballism
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Pathogenic:2
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.3251A>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, PM8, PM9, PP4, PP6 - |
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Progressive external ophthalmoplegia, proximal myopathy, and sudden death Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 1996 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Mitotip
Uncertain
Hmtvar
Pathogenic
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at