16-88709992-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001012759.3(CTU2):āc.198C>Gā(p.Asn66Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,842 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 0.000039 ( 0 hom., cov: 33)
Exomes š: 0.000068 ( 0 hom. )
Consequence
CTU2
NM_001012759.3 missense
NM_001012759.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 0.828
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31095368).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTU2 | NM_001012759.3 | c.198C>G | p.Asn66Lys | missense_variant | 3/15 | ENST00000453996.7 | |
CTU2 | NM_001318507.2 | c.198C>G | p.Asn66Lys | missense_variant | 3/15 | ||
CTU2 | NM_001012762.3 | c.198C>G | p.Asn66Lys | missense_variant | 3/14 | ||
CTU2 | NM_001318513.2 | c.-39-231C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTU2 | ENST00000453996.7 | c.198C>G | p.Asn66Lys | missense_variant | 3/15 | 1 | NM_001012759.3 | P2 | |
ENST00000616106.1 | n.446G>C | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251328Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135880
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GnomAD4 exome AF: 0.0000684 AC: 100AN: 1461632Hom.: 0 Cov.: 32 AF XY: 0.0000619 AC XY: 45AN XY: 727106
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74372
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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 | Mar 08, 2024 | The c.198C>G (p.N66K) alteration is located in exon 3 (coding exon 3) of the CTU2 gene. This alteration results from a C to G substitution at nucleotide position 198, causing the asparagine (N) at amino acid position 66 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;.
MutationTaster
Benign
D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;.
Vest4
MutPred
Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);.;
MVP
ClinPred
D
GERP RS
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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