Variant chr16-88706540-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012759.3(CTU2):c.10G>A(p.Val4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,305,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

CTU2
NM_001012759.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08201325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CTU2	NM_001012759.3 linkuse as main transcript	c.10G>A	p.Val4Met	missense_variant	1/15	ENST00000453996.7
CTU2	NM_001318507.2 linkuse as main transcript	c.10G>A	p.Val4Met	missense_variant	1/15
CTU2	NM_001012762.3 linkuse as main transcript	c.10G>A	p.Val4Met	missense_variant	1/14
CTU2	NM_001318513.2 linkuse as main transcript	c.-173G>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.10G>A	p.Val4Met	missense_variant	1/15	1	NM_001012759.3	P2	Q2VPK5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.66e-7

AC:

AN:

1305684

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

644042

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:

9.58e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 22, 2023

The c.10G>A (p.V4M) alteration is located in exon 1 (coding exon 1) of the CTU2 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the valine (V) at amino acid position 4 to be replaced by a methionine (M). 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

0.31

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0067

T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.095

T;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.45

B;P;.

Vest4

0.092

MutPred

0.14

Gain of solvent accessibility (P = 0.3956);Gain of solvent accessibility (P = 0.3956);Gain of solvent accessibility (P = 0.3956);

MVP

0.10

ClinPred

0.24

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.048

gMVP

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over