16-88707176-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting

The NM_001012759.3(CTU2):ā€‹c.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

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.35
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 Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18994987).
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00008 (117/1461608) while in subpopulation MID AF= 0.00191 (11/5766). AF 95% confidence interval is 0.00107. There are 0 homozygotes in gnomad4_exome. There are 62 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTU2NM_001012759.3 linkc.109G>C p.Val37Leu missense_variant Exon 2 of 15 ENST00000453996.7 NP_001012777.1 Q2VPK5-1
CTU2NM_001318507.2 linkc.109G>C p.Val37Leu missense_variant Exon 2 of 15 NP_001305436.1 Q2VPK5H3BSW6
CTU2NM_001012762.3 linkc.109G>C p.Val37Leu missense_variant Exon 2 of 14 NP_001012780.1 Q2VPK5-5
CTU2NM_001318513.2 linkc.-74G>C 5_prime_UTR_variant Exon 2 of 14 NP_001305442.1 Q2VPK5-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTU2ENST00000453996.7 linkc.109G>C p.Val37Leu missense_variant Exon 2 of 15 1 NM_001012759.3 ENSP00000388320.2 Q2VPK5-1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000717
AC:
18
AN:
250966
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000800
AC:
117
AN:
1461608
Hom.:
0
Cov.:
32
AF XY:
0.0000853
AC XY:
62
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000719
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.0000853
AC:
13
AN:
152342
Hom.:
0
Cov.:
33
AF XY:
0.000107
AC XY:
8
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000123
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.000382
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0084
T;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.3
M;M;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.21
Sift
Uncertain
0.029
D;T;T
Sift4G
Uncertain
0.024
D;D;D
Polyphen
0.99
D;D;.
Vest4
0.40
MVP
0.32
ClinPred
0.36
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.21
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs189839353; hg19: chr16-88773584; API