chr16-88707186-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001012759.3(CTU2):c.119T>A(p.Ile40Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000149 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
CTU2
NM_001012759.3 missense
NM_001012759.3 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 6.70
Genes affected
CTU2 (HGNC:28005): (cytosolic thiouridylase subunit 2) This gene encodes a protein which is involved in the post-transcriptional modification of transfer RNAs (tRNAs). The encoded protein plays a role in thiolation of uridine residue present at the wobble position in a subset of tRNAs, resulting in enhanced codon reading accuracy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTU2 | NM_001012759.3 | c.119T>A | p.Ile40Lys | missense_variant | 2/15 | ENST00000453996.7 | |
CTU2 | NM_001318507.2 | c.119T>A | p.Ile40Lys | missense_variant | 2/15 | ||
CTU2 | NM_001012762.3 | c.119T>A | p.Ile40Lys | missense_variant | 2/14 | ||
CTU2 | NM_001318513.2 | c.-64T>A | 5_prime_UTR_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTU2 | ENST00000453996.7 | c.119T>A | p.Ile40Lys | missense_variant | 2/15 | 1 | NM_001012759.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000175 AC: 44AN: 250926Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135832
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GnomAD4 exome AF: 0.000149 AC: 218AN: 1461598Hom.: 0 Cov.: 32 AF XY: 0.000172 AC XY: 125AN XY: 727076
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GnomAD4 genome AF: 0.000151 AC: 23AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CTU2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 18, 2023 | The CTU2 c.119T>A variant is predicted to result in the amino acid substitution p.Ile40Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.046% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-88773594-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 40 of the CTU2 protein (p.Ile40Lys). This variant is present in population databases (rs61730430, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with CTU2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MVP
ClinPred
D
GERP RS
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