chr16-88707191-G-A

Variant summary

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

The NM_001012759.3(CTU2):​c.124G>A​(p.Ala42Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,596 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 (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CTU2
NM_001012759.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.56
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]

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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=0.38946337).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTU2NM_001012759.3 linkuse as main transcriptc.124G>A p.Ala42Thr missense_variant 2/15 ENST00000453996.7
CTU2NM_001318507.2 linkuse as main transcriptc.124G>A p.Ala42Thr missense_variant 2/15
CTU2NM_001012762.3 linkuse as main transcriptc.124G>A p.Ala42Thr missense_variant 2/14
CTU2NM_001318513.2 linkuse as main transcriptc.-59G>A 5_prime_UTR_variant 2/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTU2ENST00000453996.7 linkuse as main transcriptc.124G>A p.Ala42Thr missense_variant 2/151 NM_001012759.3 P2Q2VPK5-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461596
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727072
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxDec 09, 2022In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.051
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0028
T;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.39
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.2
M;M;.
MutationTaster
Benign
0.99
D;D;D;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.24
T;T;T
Sift4G
Benign
0.25
T;T;T
Polyphen
1.0
D;P;.
Vest4
0.49
MutPred
0.63
Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);
MVP
0.54
ClinPred
0.97
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1339742213; hg19: chr16-88773599; API