16-88707120-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001012759.3(CTU2):c.69-16C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,611,542 control chromosomes in the GnomAD database, including 56,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3650 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52537 hom.)
• Consequence: CTU2 NM_001012759.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.560

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-88707120-C-A is Benign according to our data. Variant chr16-88707120-C-A is described in ClinVar as [Benign]. Clinvar id is 1253335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTU2	NM_001012759.3	c.69-16C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000453996.7
CTU2	NM_001012762.3	c.69-16C>A		splice_polypyrimidine_tract_variant, intron_variant
CTU2	NM_001318507.2	c.69-16C>A		splice_polypyrimidine_tract_variant, intron_variant
CTU2	NM_001318513.2	c.-114-16C>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTU2	ENST00000453996.7	c.69-16C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001012759.3	P2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29420 AN: 151992 Hom.: 3651 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.219

GnomAD3 exomes AF: 0.218 AC: 54667 AN: 250640 Hom.: 7242 AF XY: 0.230 AC XY: 31174 AN XY: 135696

Gnomad AFR exome AF: 0.0467

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.0258

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.260 AC: 378972 AN: 1459432 Hom.: 52537 Cov.: 32 AF XY: 0.262 AC XY: 190195 AN XY: 725804

Gnomad4 AFR exome AF: 0.0422

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.0169

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.193 AC: 29417 AN: 152110 Hom.: 3650 Cov.: 32 AF XY: 0.190 AC XY: 14149 AN XY: 74350

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.0257

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.217

Alfa AF: 0.191 Hom.: 656

Bravo AF: 0.181

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2020	- -

CTU2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 27, 2023

This variant is classified as 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	-0.89
Cadd	Benign	1.1
Dann	Benign	0.70

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

Other links and lift over

dbSNP: rs11641194; hg19: chr16-88773528;