Genetic Variant CTU1:p.Arg314His (chr19-51098707-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_145232.4(CTU1):c.941G>A(p.Arg314His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,740 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTU1
NM_145232.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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 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=0.29912788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU1	NM_145232.4 link	c.941G>A	p.Arg314His	missense_variant	Exon 3 of 3	ENST00000421832.3	NP_660275.2	Q7Z7A3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU1	ENST00000421832.3 link	c.941G>A	p.Arg314His	missense_variant	Exon 3 of 3	2	NM_145232.4	ENSP00000390011.1		Q7Z7A3

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150740

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000108

AC:

AN:

1115512

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

536390

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000129

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73614

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.941G>A (p.R314H) alteration is located in exon 3 (coding exon 2) of the CTU1 gene. This alteration results from a G to A substitution at nucleotide position 941, causing the arginine (R) at amino acid position 314 to be replaced by a histidine (H). 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

0.21

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.29

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.10

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.12

MutPred

0.40

Loss of methylation at R314 (P = 0.0087);

MVP

0.33

MPC

1.8

ClinPred

0.42

GERP RS

3.0

Varity_R

0.26

gMVP

0.44

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