rs398122419
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The ENST00000498286.6(MTO1):c.1232C>T(p.Thr411Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
MTO1
ENST00000498286.6 missense
ENST00000498286.6 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 7.39
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.98
PP5
Variant 6-73480777-C-T is Pathogenic according to our data. Variant chr6-73480777-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 89038.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-73480777-C-T is described in Lovd as [Pathogenic]. Variant chr6-73480777-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTO1 | NM_012123.4 | c.1232C>T | p.Thr411Ile | missense_variant | 7/12 | ENST00000498286.6 | NP_036255.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTO1 | ENST00000498286.6 | c.1232C>T | p.Thr411Ile | missense_variant | 7/12 | 1 | NM_012123.4 | ENSP00000419561 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251460Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135906
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461814Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727214
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74254
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;.;.;H
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;.;D
Vest4
MutPred
0.89
.;.;.;Loss of glycosylation at T436 (P = 0.0205);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at