Genetic Variant CTU1:p.Pro284Ser (chr19-51098798-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145232.4(CTU1):c.850C>T(p.Pro284Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000516 in 1,046,558 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

CTU1
NM_145232.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057663232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU1	NM_145232.4 link	c.850C>T	p.Pro284Ser	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.850C>T	p.Pro284Ser	missense_variant	Exon 3 of 3	2	NM_145232.4	ENSP00000390011.1		Q7Z7A3

Frequencies

GnomAD3 genomes

AF:

0.0000954

AC:

AN:

146782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000454

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

899710

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

421430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16914

American (AMR)

AF:

0.00

AC:

AN:

2928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6876

East Asian (EAS)

AF:

0.00

AC:

AN:

8748

South Asian (SAS)

AF:

0.00165

AC:

AN:

17580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1966

European-Non Finnish (NFE)

AF:

0.00000870

AC:

AN:

804178

Other (OTH)

AF:

0.000128

AC:

AN:

31142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000953

AC:

AN:

146848

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

71472

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

41018

American (AMR)

AF:

0.00

AC:

AN:

14796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000454

AC:

AN:

66020

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.850C>T (p.P284S) 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 850, causing the proline (P) at amino acid position 284 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

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0077

Eigen

Benign

0.037

Eigen_PC

Benign

0.0053

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.55

M_CAP

Benign

0.052

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

3.6

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.20

REVEL

Benign

0.12

Sift

Benign

0.74

Sift4G

Benign

0.45

Polyphen

0.94

Vest4

0.13

MutPred

0.32

Gain of helix (P = 0.0143);

MVP

0.28

MPC

1.3

ClinPred

0.83

GERP RS

3.2

Varity_R

0.086

gMVP

0.48

Mutation Taster

=84/16

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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19-51098798-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over