Variant 19-51098612-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145232.4(CTU1):c.1036C>T(p.Pro346Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,301,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CTU1
NM_145232.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.262

Variant links:

Genes affected

CTU1 (HGNC:29590): (cytosolic thiouridylase subunit 1) Predicted to enable tRNA binding activity. Predicted to be involved in tRNA wobble position uridine thiolation. Predicted to be located in cytosol. Predicted to be part of cytosolic tRNA wobble base thiouridylase complex. [provided by Alliance of Genome Resources, Apr 2022]

CTU1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017155826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTU1	NM_145232.4 linkuse as main transcript	c.1036C>T	p.Pro346Ser	missense_variant	3/3	ENST00000421832.3	NP_660275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTU1	ENST00000421832.3 linkuse as main transcript	c.1036C>T	p.Pro346Ser	missense_variant	3/3	2	NM_145232.4	ENSP00000390011	P1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

189

AN:

1149274

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

AN XY:

552710

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00689

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000209

Gnomad4 OTH exome

AF:

0.0000649

GnomAD4 genome

AF:

0.000131

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000268

ExAC

AF:

0.000305

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2022

The c.1036C>T (p.P346S) alteration is located in exon 3 (coding exon 2) of the CTU1 gene. This alteration results from a C to T substitution at nucleotide position 1036, causing the proline (P) at amino acid position 346 to be replaced by a serine (S). 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

0.097

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0068

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.29

M_CAP

Benign

0.019

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

0.20

REVEL

Benign

0.022

Sift

Uncertain

0.020

Sift4G

Uncertain

0.016

Polyphen

0.027

Vest4

0.047

MutPred

0.20

Gain of phosphorylation at P346 (P = 0.0174);

MVP

0.067

MPC

1.0

ClinPred

0.075

GERP RS

0.80

Varity_R

0.029

gMVP

0.51

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