16-88706555-G-A

Position:

chr16-88706555-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CTU2	NM_001012759.3 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	1/15	ENST00000453996.7
CTU2	NM_001318507.2 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	1/15
CTU2	NM_001012762.3 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	1/14
CTU2	NM_001318513.2 linkuse as main transcript	c.-158G>A		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTU2	ENST00000453996.7 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	1/15	1	NM_001012759.3	P2	Q2VPK5-1

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

GnomAD3 exomes

AF:

0.0152

AC:

1069

AN:

70398

Hom.:

AF XY:

0.0156

AC XY:

642

AN XY:

41208

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 SAS exome

AF:

0.0106

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

Gnomad4 AFR exome

AF:

0.00241

Gnomad4 AMR exome

AF:

0.00960

Gnomad4 ASJ exome

AF:

0.0227

Gnomad4 EAS exome

AF:

0.0000355

Gnomad4 SAS exome

AF:

0.00938

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0206

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0135

AC:

2054

AN:

152140

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

949

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0237

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.00802

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00869

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CTU2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

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

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;.

MutationTaster

Benign

1.0

D;N;N;N

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.077

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over