M-10455-A-G
Variant names:
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
Mitomap GenBank:
𝑓 0.00020 ( AC: 12 )
Consequence
TRNR
missense
missense
Scores
Mitotip
Benign
Clinical Significance
No linked disesase in Mitomap
Conservation
PhyloP100: -1.88
Genes affected
TRNR (HGNC:7496): (mitochondrially encoded tRNA arginine)
ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP6
Variant M-10455-A-G is Benign according to our data. Variant chrM-10455-A-G is described in ClinVar as [Uncertain_significance]. Clinvar id is 690123.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS2
High AC in GnomadMitoHomoplasmic at 16
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
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
AC:
12
Gnomad homoplasmic
AF:
AC:
16
AN:
56432
Gnomad heteroplasmic
AF:
AC:
0
AN:
56432
Alfa
AF:
Hom.:
Mitomap
No disease associated.
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Benign:1
Revision: reviewed by expert panel
LINK: link
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.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
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.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:
Name
Calibrated prediction
Score
Prediction
Mitotip
Benign
Hmtvar
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at