rs773023974

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018006.5(TRMU):​c.1135G>A​(p.Gly379Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRMU
NM_018006.5 missense

Scores

7
2
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.84
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRMUNM_018006.5 linkc.1135G>A p.Gly379Ser missense_variant Exon 11 of 11 ENST00000645190.1 NP_060476.2 O75648-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRMUENST00000645190.1 linkc.1135G>A p.Gly379Ser missense_variant Exon 11 of 11 NM_018006.5 ENSP00000496496.1 O75648-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461132
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Benign
-0.0012
T
BayesDel_noAF
Benign
-0.24
CADD
Pathogenic
30
DANN
Uncertain
1.0
Eigen
Pathogenic
0.97
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.48
T;T
M_CAP
Pathogenic
0.76
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Pathogenic
1.1
D
PROVEAN
Benign
-1.3
N;.
REVEL
Uncertain
0.55
Sift
Benign
0.086
T;.
Sift4G
Benign
0.076
T;.
Polyphen
0.50
P;.
Vest4
0.62
MutPred
0.55
Loss of sheet (P = 0.0025);.;
MVP
0.80
ClinPred
1.0
D
GERP RS
4.3
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-46752772; API