16-88707117-C-T

Variant names:

• chr16-88707117-C-T
• rs185353598
• NM_001012759.3:c.69-19C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00365 (556/152260) while in subpopulation NFE AF = 0.00594 (404/68016). AF 95% confidence interval is 0.00546. There are 3 homozygotes in GnomAd4. There are 238 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.69-19C>T		intron_variant	Intron 1 of 14	ENST00000453996.7	NP_001012777.1
CTU2	NM_001318507.2	c.69-19C>T		intron_variant	Intron 1 of 14		NP_001305436.1
CTU2	NM_001012762.3	c.69-19C>T		intron_variant	Intron 1 of 13		NP_001012780.1
CTU2	NM_001318513.2	c.-114-19C>T		intron_variant	Intron 1 of 13		NP_001305442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7	c.69-19C>T		intron_variant	Intron 1 of 14	1	NM_001012759.3	ENSP00000388320.2

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

GnomAD2 exomes AF: 0.00371 AC: 929 AN: 250740 AF XY: 0.00356

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 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

African (AFR) AF: 0.000837 AC: 28 AN: 33452

American (AMR) AF: 0.00291 AC: 130 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39636

South Asian (SAS) AF: 0.00367 AC: 316 AN: 86216

European-Finnish (FIN) AF: 0.00117 AC: 62 AN: 53198

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5764

European-Non Finnish (NFE) AF: 0.00574 AC: 6376 AN: 1110426

Other (OTH) AF: 0.00464 AC: 280 AN: 60320

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

African (AFR) AF: 0.000842 AC: 35 AN: 41558

American (AMR) AF: 0.00262 AC: 40 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4822

European-Finnish (FIN) AF: 0.000943 AC: 10 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00594 AC: 404 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

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

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Nov 18, 2021

Fulgent Genetics, Fulgent Genetics

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	-0.88
CADD	Benign	1.5
DANN	Benign	0.82
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs185353598; hg19: chr16-88773525;