Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP4_StrongBP6_Very_Strong
The NM_012123.4(MTO1):āc.176G>Cā(p.Gly59Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000715 in 1,614,048 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G59C) has been classified as Uncertain significance.
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]
PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
Multiple lines of computational evidence support a deleterious effect 8: BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.028492749).
BP6
?
BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-73462030-G-C is Benign according to our data. Variant chr6-73462030-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 540425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency Benign:1
Benign, criteria provided, single submitter
clinical testing
Invitae
Jan 04, 2024
- -
not provided Benign:1
Likely benign, criteria provided, single submitter
clinical testing
GeneDx
May 26, 2020
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22494076) -