16-88709992-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001012759.3(CTU2):ā€‹c.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

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.828
Variant links:
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]

Genome browser will be placed here

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
CTU2NM_001012759.3 linkuse as main transcriptc.198C>G p.Asn66Lys missense_variant 3/15 ENST00000453996.7
CTU2NM_001318507.2 linkuse as main transcriptc.198C>G p.Asn66Lys missense_variant 3/15
CTU2NM_001012762.3 linkuse as main transcriptc.198C>G p.Asn66Lys missense_variant 3/14
CTU2NM_001318513.2 linkuse as main transcriptc.-39-231C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTU2ENST00000453996.7 linkuse as main transcriptc.198C>G p.Asn66Lys missense_variant 3/151 NM_001012759.3 P2Q2VPK5-1
ENST00000616106.1 linkuse as main transcriptn.446G>C non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251328
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000684
AC:
100
AN:
1461632
Hom.:
0
Cov.:
32
AF XY:
0.0000619
AC XY:
45
AN XY:
727106
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:
0.0000809
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsMar 08, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.033
T;.;.;.
Eigen
Benign
0.069
Eigen_PC
Benign
-0.013
FATHMM_MKL
Benign
0.76
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Pathogenic
3.2
M;M;.;.
MutationTaster
Benign
0.99
D;D;D;N
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.4
D;D;D;D
REVEL
Benign
0.27
Sift
Uncertain
0.011
D;D;D;D
Sift4G
Uncertain
0.015
D;D;D;D
Polyphen
0.99
D;D;.;.
Vest4
0.66
MutPred
0.64
Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);.;
MVP
0.36
ClinPred
0.61
D
GERP RS
0.71
Varity_R
0.44
gMVP
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760949995; hg19: chr16-88776400; API