16-88707176-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001012759.3(CTU2):āc.109G>Cā(p.Val37Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 33)
Exomes š: 0.000080 ( 0 hom. )
Consequence
CTU2
NM_001012759.3 missense
NM_001012759.3 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 8.35
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18994987).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTU2 | NM_001012759.3 | c.109G>C | p.Val37Leu | missense_variant | 2/15 | ENST00000453996.7 | |
CTU2 | NM_001318507.2 | c.109G>C | p.Val37Leu | missense_variant | 2/15 | ||
CTU2 | NM_001012762.3 | c.109G>C | p.Val37Leu | missense_variant | 2/14 | ||
CTU2 | NM_001318513.2 | c.-74G>C | 5_prime_UTR_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTU2 | ENST00000453996.7 | c.109G>C | p.Val37Leu | missense_variant | 2/15 | 1 | NM_001012759.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000717 AC: 18AN: 250966Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135838
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GnomAD4 exome AF: 0.0000800 AC: 117AN: 1461608Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62AN XY: 727080
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GnomAD4 genome AF: 0.0000853 AC: 13AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74504
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.109G>C (p.V37L) alteration is located in exon 2 (coding exon 2) of the CTU2 gene. This alteration results from a G to C substitution at nucleotide position 109, causing the valine (V) at amino acid position 37 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;T;T
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MVP
ClinPred
T
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