Genetic Variant CTU2:c.1420-15C>T (chr16-88715033-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001012759.3(CTU2):c.1420-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,577,188 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 (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

CTU2
NM_001012759.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.09

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 Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-88715033-C-T is Benign according to our data. Variant chr16-88715033-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3627546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000276 (42/152310) while in subpopulation AFR AF= 0.000601 (25/41566). AF 95% confidence interval is 0.000418. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3 link	c.1420-15C>T	intron_variant	Intron 13 of 14	ENST00000453996.7	NP_001012777.1	Q2VPK5-1
CTU2	NM_001318507.2 link	c.1633-15C>T	intron_variant	Intron 13 of 14		NP_001305436.1	Q2VPK5H3BSW6
CTU2	NM_001012762.3 link	c.1419+107C>T	intron_variant	Intron 13 of 13		NP_001012780.1	Q2VPK5-5
CTU2	NM_001318513.2 link	c.1159-15C>T	intron_variant	Intron 12 of 13		NP_001305442.1	Q2VPK5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7 link	c.1420-15C>T		intron_variant	Intron 13 of 14	1	NM_001012759.3	ENSP00000388320.2		Q2VPK5-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000292

AC:

AN:

212436

Hom.:

AF XY:

0.000242

AC XY:

AN XY:

115646

show subpopulations

Gnomad AFR exome

AF:

0.000513

Gnomad AMR exome

AF:

0.000477

Gnomad ASJ exome

AF:

0.000262

Gnomad EAS exome

AF:

0.000353

Gnomad SAS exome

AF:

0.0000787

Gnomad FIN exome

AF:

0.000298

Gnomad NFE exome

AF:

0.000231

Gnomad OTH exome

AF:

0.000573

GnomAD4 exome

AF:

0.000171

AC:

244

AN:

1424878

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

107

AN XY:

704746

show subpopulations

Gnomad4 AFR exome

AF:

0.000759

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.000206

Gnomad4 EAS exome

AF:

0.0000772

Gnomad4 SAS exome

AF:

0.0000975

Gnomad4 FIN exome

AF:

0.000230

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.000276

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.000276

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0090

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over