rs137933845

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001012759.3(CTU2):c.25G>A(p.Gly9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,458,604 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 22 hom., cov: 33)

Exomes 𝑓: 0.019 ( 250 hom. )

Consequence

CTU2
NM_001012759.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.792

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023970008).

BP6

Variant 16-88706555-G-A is Benign according to our data. Variant chr16-88706555-G-A is described in ClinVar as [Benign]. Clinvar id is 1529311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0135 (2054/152140) while in subpopulation NFE AF = 0.0215 (1458/67950). AF 95% confidence interval is 0.0205. There are 22 homozygotes in GnomAd4. There are 949 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3 link	c.25G>A	p.Gly9Arg	missense_variant	Exon 1 of 15	ENST00000453996.7	NP_001012777.1	Q2VPK5-1
RNF166	NM_178841.4 link	c.-230C>T		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.25G>A	p.Gly9Arg	missense_variant	Exon 1 of 15	1	NM_001012759.3	ENSP00000388320.2		Q2VPK5-1
RNF166	ENST00000312838.9 link	c.-230C>T		upstream_gene_variant		1	NM_178841.4	ENSP00000326095.4		Q96A37-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2055

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.00802

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.0152

AC:

1069

AN:

70398

AF XY:

0.0156

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00772

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.0211

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0186

AC:

24330

AN:

1306464

Hom.:

250

Cov.:

AF XY:

0.0184

AC XY:

11835

AN XY:

644460

show subpopulations

African (AFR)

AF:

0.00241

AC:

AN:

26130

American (AMR)

AF:

0.00960

AC:

223

AN:

23238

Ashkenazi Jewish (ASJ)

AF:

0.0227

AC:

518

AN:

22788

East Asian (EAS)

AF:

0.0000355

AC:

AN:

28144

South Asian (SAS)

AF:

0.00938

AC:

669

AN:

71350

European-Finnish (FIN)

AF:

0.0112

AC:

367

AN:

32688

Middle Eastern (MID)

AF:

0.0224

AC:

AN:

3922

European-Non Finnish (NFE)

AF:

0.0206

AC:

21476

AN:

1044164

Other (OTH)

AF:

0.0171

AC:

925

AN:

54040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1209

2418

3626

4835

6044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0135

AC:

2054

AN:

152140

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

949

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00327

AC:

136

AN:

41538

American (AMR)

AF:

0.0133

AC:

204

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0237

AC:

AN:

3464

East Asian (EAS)

AF:

0.000194

AC:

AN:

5144

South Asian (SAS)

AF:

0.00870

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00802

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0215

AC:

1458

AN:

67950

Other (OTH)

AF:

0.0156

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0134

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0127

AC:

ExAC

AF:

0.00614

AC:

427

Asia WGS

AF:

0.00232

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CTU2-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0053

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00018

LIST_S2

Benign

0.67

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.61

N;N;.

PhyloP100

-0.79

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0060

B;B;.

Vest4

0.015

MutPred

0.10

Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);

ClinPred

0.0044

GERP RS

1.1

PromoterAI

-0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.077

gMVP

0.29

Mutation Taster

=299/1

polymorphism

(source)

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

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rs137933845

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over