Genetic Variant CTU2:p.Pro16Ala (chr16-88706576-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012759.3(CTU2):c.46C>G(p.Pro16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000768 in 1,302,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P16S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

CTU2
NM_001012759.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.466

Publications

0 publications found

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]

CTU2 links:

RNF166 (HGNC:28856): (ring finger protein 166) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNF166 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06807786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3 link	c.46C>G	p.Pro16Ala	missense_variant	Exon 1 of 15	ENST00000453996.7	NP_001012777.1	Q2VPK5-1
RNF166	NM_178841.4 link	c.-251G>C		upstream_gene_variant		ENST00000312838.9	NP_849163.1	Q96A37-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7 link	c.46C>G	p.Pro16Ala	missense_variant	Exon 1 of 15	1	NM_001012759.3	ENSP00000388320.2		Q2VPK5-1
RNF166	ENST00000312838.9 link	c.-251G>C		upstream_gene_variant		1	NM_178841.4	ENSP00000326095.4		Q96A37-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.68e-7

AC:

AN:

1302856

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

642630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25916

American (AMR)

AF:

0.00

AC:

AN:

22322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22616

East Asian (EAS)

AF:

0.00

AC:

AN:

28192

South Asian (SAS)

AF:

0.00

AC:

AN:

70782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3872

European-Non Finnish (NFE)

AF:

9.59e-7

AC:

AN:

1042688

Other (OTH)

AF:

0.00

AC:

AN:

53878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.4

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.027

T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.00030

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;L;.

PhyloP100

-0.47

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.034

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.16

T;T;D

Polyphen

0.13

B;B;.

Vest4

0.14

MutPred

0.25

Loss of catalytic residue at P16 (P = 0.0034);Loss of catalytic residue at P16 (P = 0.0034);Loss of catalytic residue at P16 (P = 0.0034);

MVP

0.18

ClinPred

0.055

GERP RS

2.2

PromoterAI

0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.040

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over