M-10455-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_StrongBS2
Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Consequence
missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRNR | unassigned_transcript_4809 | c.51A>G | p.Ile17Met | missense_variant | Exon 1 of 1 | |||
ND4L | unassigned_transcript_4810 | c.-15A>G | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|
Frequencies
GnomAD4 exome Cov.: 0
Mitomap
ClinVar
Submissions by phenotype
Mitochondrial disease Uncertain:1
The m.10455A>G variant in MT-TR 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). This variant has been reported only once in the literature (PMID: 23463613; Supp Table S1B) in the homoplasmic state in an individual from H haplogroup and mother was not available for testing. This does not meet criteria for PS4_supporting which requires at least two unrelated affected individuals. There are no large families reported in the medical literature to consider for evidence of segregation. There are several occurrences of this variant in GenBank sequences queried through MITOMAP on 6/29/2020 (seen in 1-4 individuals from several haplogroups including J1c, H1b, H1j, U5a, N1a for a total of 12/51,192 frequency). The computational predictor MitoTIP suggests this variant is likely benign (10th percentile) and HmtVAR predicts it to be likely polymorphic (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. -
MELAS syndrome Benign:1
The NC_012920.1:m.10455A>G variant in MT-TR gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at