16-88706528-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001012759.3(CTU2):​c.-3C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,449,456 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

CTU2
NM_001012759.3 5_prime_UTR

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.284
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 16-88706528-C-G is Benign according to our data. Variant chr16-88706528-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3035852.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTU2NM_001012759.3 linkuse as main transcriptc.-3C>G 5_prime_UTR_variant 1/15 ENST00000453996.7
CTU2NM_001012762.3 linkuse as main transcriptc.-3C>G 5_prime_UTR_variant 1/14
CTU2NM_001318507.2 linkuse as main transcriptc.-3C>G 5_prime_UTR_variant 1/15
CTU2NM_001318513.2 linkuse as main transcriptc.-185C>G 5_prime_UTR_variant 1/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTU2ENST00000453996.7 linkuse as main transcriptc.-3C>G 5_prime_UTR_variant 1/151 NM_001012759.3 P2Q2VPK5-1

Frequencies

GnomAD3 genomes
AF:
0.000526
AC:
80
AN:
152126
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00183
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000154
AC:
1
AN:
65110
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
38576
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000918
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000555
AC:
72
AN:
1297222
Hom.:
0
Cov.:
31
AF XY:
0.0000578
AC XY:
37
AN XY:
639754
show subpopulations
Gnomad4 AFR exome
AF:
0.00233
Gnomad4 AMR exome
AF:
0.000189
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:
0.00000192
Gnomad4 OTH exome
AF:
0.000112
GnomAD4 genome
AF:
0.000526
AC:
80
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.000484
AC XY:
36
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.00183
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000641
Hom.:
0
Bravo
AF:
0.000763
Asia WGS
AF:
0.000290
AC:
1
AN:
3460

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

CTU2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 30, 2019This variant is classified as likely 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
BayesDel_noAF
Benign
-0.48
CADD
Benign
5.8
DANN
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs570424055; hg19: chr16-88772936; API