rs587776436
Variant summary
Our verdict is Uncertain significance. Variant got -1 ACMG points: 0P and 1B. BP4
This summary comes from the ClinGen Evidence Repository: The m.5558A>G variant in MT-TW was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID:32906214). There have been no affected individuals reported in the medical literature to our knowledge. There are no large families reported in the medical literature to consider for evidence of segregation. There are over 100 occurrences in MITOMAP for an overall allele frequency of 0.2%. This does not meet criteria for BA1 or BS1. The computational predictor MitoTIP suggests this variant is possibly benign (31st percentile) and HmtVAR predicts it to be likely polymorphic (0.5, BP4). There are no cybrid or single fiber studies reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA414780655/MONDO:0044970/014
Frequency
Consequence
ENST00000387382.1 non_coding_transcript_exon
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRNW | TRNW.1 use as main transcript | n.47A>G | non_coding_transcript_exon_variant | 1/1 | |||
TRNA | TRNA.1 use as main transcript | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-TW | ENST00000387382.1 | n.47A>G | 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
Mitomap
ClinVar
Submissions by phenotype
Mitochondrial disease Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | Dec 10, 2021 | The m.5558A>G variant in MT-TW was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). There have been no affected individuals reported in the medical literature to our knowledge. There are no large families reported in the medical literature to consider for evidence of segregation. There are over 100 occurrences in MITOMAP for an overall allele frequency of 0.2%. This does not meet criteria for BA1 or BS1. The computational predictor MitoTIP suggests this variant is possibly benign (31st percentile) and HmtVAR predicts it to be likely polymorphic (0.5, BP4). There are no cybrid or single fiber studies reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BP4. - |
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1
Benign, 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.5558A>G variant in MT-TW gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4, BP5 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at