19-51099032-C-T

Variant summary

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

The NM_145232.4(CTU1):​c.616G>A​(p.Ala206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,507,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

CTU1
NM_145232.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40
Variant links:
Genes affected
CTU1 (HGNC:29590): (cytosolic thiouridylase subunit 1) Predicted to enable tRNA binding activity. Predicted to be involved in tRNA wobble position uridine thiolation. Predicted to be located in cytosol. Predicted to be part of cytosolic tRNA wobble base thiouridylase complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.26615968).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTU1NM_145232.4 linkc.616G>A p.Ala206Thr missense_variant Exon 3 of 3 ENST00000421832.3 NP_660275.2 Q7Z7A3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTU1ENST00000421832.3 linkc.616G>A p.Ala206Thr missense_variant Exon 3 of 3 2 NM_145232.4 ENSP00000390011.1 Q7Z7A3

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151620
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000737
AC:
10
AN:
1356274
Hom.:
0
Cov.:
31
AF XY:
0.00000745
AC XY:
5
AN XY:
670732
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000302
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000846
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151620
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74054
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:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.616G>A (p.A206T) alteration is located in exon 3 (coding exon 2) of the CTU1 gene. This alteration results from a G to A substitution at nucleotide position 616, causing the alanine (A) at amino acid position 206 to be replaced by a threonine (T). 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
Benign
0.11
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0022
T
Eigen
Benign
0.15
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.86
N
REVEL
Benign
0.061
Sift
Benign
0.59
T
Sift4G
Benign
0.43
T
Polyphen
1.0
D
Vest4
0.17
MVP
0.24
MPC
1.3
ClinPred
0.73
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.11
gMVP
0.42

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: rs996215928; hg19: chr19-51602289; API