Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_012123.4(MTO1):c.922A>G(p.Thr308Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00281 in 1,613,106 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
MTO1 (HGNC:19261): (mitochondrial tRNA translation optimization 1) This gene encodes a mitochondrial protein thought to be involved in mitochondrial tRNA modification. The encoded protein may also play a role in the expression of the non-syndromic and aminoglycoside-induced deafness phenotypes associated with a specific mutation in the mitochondrial 12S rRNA gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Computational evidence support a benign effect (MetaRNN=0.011800498).
BP6
Variant 6-73479828-A-G is Benign according to our data. Variant chr6-73479828-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 240850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00187 (285/152318) while in subpopulation NFE AF= 0.00341 (232/68034). AF 95% confidence interval is 0.00305. There are 0 homozygotes in gnomad4. There are 131 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant is associated with the following publications: (PMID: 22494076) -
Mar 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
MTO1: BS2 -
Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency Benign:3
Jan 01, 2019
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: PP3,BS2,BS6. -
Dec 05, 2022
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: research
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Jan 30, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
MTO1-related disorder Benign:1
Apr 09, 2021
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -