rs190598648

Variant names:

• chr16-88715033-C-T
• rs190598648
• NM_001012759.3:c.1420-15C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88715033-C-T
• chr16-88715033-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.09
• Publications: 0 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 -10 ACMG points.

• 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012759.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU2	NM_001012759.3	MANE Select	c.1420-15C>T		intron	N/A	NP_001012777.1	Q2VPK5-1
	CTU2	NM_001318507.2		c.1633-15C>T		intron	N/A	NP_001305436.1	H3BSW6
	CTU2	NM_001012762.3		c.1419+107C>T		intron	N/A	NP_001012780.1	Q2VPK5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU2	ENST00000453996.7	TSL:1 MANE Select	c.1420-15C>T		intron	N/A	ENSP00000388320.2	Q2VPK5-1
	CTU2	ENST00000567949.5	TSL:1	c.1633-15C>T		intron	N/A	ENSP00000456908.1	H3BSW6
	CTU2	ENST00000564105.5	TSL:1	n.*1131-15C>T		intron	N/A	ENSP00000454923.1	H3BNM3

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152192 Hom.: 0 Cov.: 34

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

GnomAD2 exomes AF: 0.000292 AC: 62 AN: 212436 AF XY: 0.000242

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 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.: 0 Cov.: 64 AF XY: 0.000152 AC XY: 107 AN XY: 704746

African (AFR) AF: 0.000759 AC: 25 AN: 32954

American (AMR) AF: 0.000380 AC: 16 AN: 42152

Ashkenazi Jewish (ASJ) AF: 0.000206 AC: 5 AN: 24228

East Asian (EAS) AF: 0.0000772 AC: 3 AN: 38860

South Asian (SAS) AF: 0.0000975 AC: 8 AN: 82034

European-Finnish (FIN) AF: 0.000230 AC: 11 AN: 47738

Middle Eastern (MID) AF: 0.000888 AC: 5 AN: 5630

European-Non Finnish (NFE) AF: 0.000148 AC: 162 AN: 1092468

Other (OTH) AF: 0.000153 AC: 9 AN: 58814

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152310 Hom.: 0 Cov.: 34 AF XY: 0.000228 AC XY: 17 AN XY: 74472

African (AFR) AF: 0.000601 AC: 25 AN: 41566

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.000276

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0090
DANN	Benign	0.68
PhyloP100		-5.1
PromoterAI		-0.0046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs190598648; hg19: chr16-88781441;