rs118203992
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_018006.5(TRMU):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
TRMU
NM_018006.5 start_lost
NM_018006.5 start_lost
Scores
4
4
7
Clinical Significance
Conservation
PhyloP100: 2.03
Genes affected
TRMU (HGNC:25481): (tRNA mitochondrial 2-thiouridylase) This nuclear gene encodes a mitochondrial tRNA-modifying enzyme. The encoded protein catalyzes the 2-thiolation of uridine on the wobble positions of tRNA(Lys), tRNA(Glu), and tRNA(Gln), resulting in the formation of 5-taurinomethyl-2-thiouridine moieties. Mutations in this gene may cause transient infantile liver failure. Polymorphisms in this gene may also influence the severity of deafness caused by mitochondrial 12S ribosomal RNA mutations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_018006.5 (TRMU) was described as [Conflicting_classifications_of_pathogenicity] in ClinVar as 215292
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 22-46335766-T-A is Pathogenic according to our data. Variant chr22-46335766-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 1294.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRMU | NM_018006.5 | c.2T>A | p.Met1? | start_lost | 1/11 | ENST00000645190.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRMU | ENST00000645190.1 | c.2T>A | p.Met1? | start_lost | 1/11 | NM_018006.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
A;A
PROVEAN
Benign
N;.;.;N
REVEL
Uncertain
Sift
Uncertain
D;.;.;D
Sift4G
Uncertain
D;.;.;D
Polyphen
D;D;.;P
Vest4
MutPred
Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at