16-88707117-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001012759.3(CTU2):c.69-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00482 in 1,612,104 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (19 hom.)
• Consequence: CTU2 NM_001012759.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.715

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-88707117-C-T is Benign according to our data. Variant chr16-88707117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1600007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTU2	NM_001012759.3	c.69-19C>T		intron_variant		ENST00000453996.7
CTU2	NM_001012762.3	c.69-19C>T		intron_variant
CTU2	NM_001318507.2	c.69-19C>T		intron_variant
CTU2	NM_001318513.2	c.-114-19C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTU2	ENST00000453996.7	c.69-19C>T		intron_variant		1	NM_001012759.3	P2

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 556 AN: 152142 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00594

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00371 AC: 929 AN: 250740 Hom.: 7 AF XY: 0.00356 AC XY: 484 AN XY: 135782

Gnomad AFR exome AF: 0.000680

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00340

Gnomad FIN exome AF: 0.000785

Gnomad NFE exome AF: 0.00581

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00494 AC: 7217 AN: 1459844 Hom.: 19 Cov.: 30 AF XY: 0.00485 AC XY: 3521 AN XY: 726036

Gnomad4 AFR exome AF: 0.000837

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00367

Gnomad4 FIN exome AF: 0.00117

Gnomad4 NFE exome AF: 0.00574

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.00365 AC: 556 AN: 152260 Hom.: 3 Cov.: 33 AF XY: 0.00320 AC XY: 238 AN XY: 74430

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000943

Gnomad4 NFE AF: 0.00594

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00374

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.5
Dann	Benign	0.82

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: rs185353598; hg19: chr16-88773525;