16-88714227-GGTGT-GGTGTGTGTGGGTGTGTGT

Variant names:

• chr16-88714227-G-GGTGTGTGTGGGTGT
• rs149847195
• NM_001012759.3:c.1097+5_1097+6insTGTGGGTGTGTGTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001012759.3(CTU2):​c.1097+5_1097+6insTGTGGGTGTGTGTG variant causes a splice region, intron change. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: CTU2 NM_001012759.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000426 (18/42292) while in subpopulation AFR AF = 0.00101 (17/16840). AF 95% confidence interval is 0.000643. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 0. 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU2	NM_001012759.3	MANE Select	c.1097+5_1097+6insTGTGGGTGTGTGTG		splice_region intron	N/A	NP_001012777.1
	CTU2	NM_001318507.2		c.1310+5_1310+6insTGTGGGTGTGTGTG		splice_region intron	N/A	NP_001305436.1
	CTU2	NM_001012762.3		c.1097+5_1097+6insTGTGGGTGTGTGTG		splice_region intron	N/A	NP_001012780.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU2	ENST00000453996.7	TSL:1 MANE Select	c.1097_1097+1insGTGTGTGTGGGTGT		splice_donor intron	N/A	ENSP00000388320.2
	CTU2	ENST00000567949.5	TSL:1	c.1310_1310+1insGTGTGTGTGGGTGT		splice_donor intron	N/A	ENSP00000456908.1
	CTU2	ENST00000564105.5	TSL:1	n.*808_*808+1insGTGTGTGTGGGTGT		splice_donor intron	N/A	ENSP00000454923.1

Frequencies

GnomAD3 genomes AF: 0.000402 AC: 17 AN: 42254 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000473

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000322 AC: 8 AN: 248558 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000311

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000505 AC: 19 AN: 376376 Hom.: 0 Cov.: 0 AF XY: 0.0000438 AC XY: 8 AN XY: 182760

African (AFR) AF: 0.000807 AC: 11 AN: 13634

American (AMR) AF: 0.00 AC: 0 AN: 5120

Ashkenazi Jewish (ASJ) AF: 0.000182 AC: 1 AN: 5490

East Asian (EAS) AF: 0.00 AC: 0 AN: 228

South Asian (SAS) AF: 0.00 AC: 0 AN: 6878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 388

European-Non Finnish (NFE) AF: 0.0000222 AC: 7 AN: 315144

Other (OTH) AF: 0.00 AC: 0 AN: 13934

GnomAD4 genome AF: 0.000426 AC: 18 AN: 42292 Hom.: 0 Cov.: 0 AF XY: 0.000299 AC XY: 6 AN XY: 20062

African (AFR) AF: 0.00101 AC: 17 AN: 16840

American (AMR) AF: 0.000473 AC: 1 AN: 2114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 758

East Asian (EAS) AF: 0.00 AC: 0 AN: 52

South Asian (SAS) AF: 0.00 AC: 0 AN: 360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 18438

Other (OTH) AF: 0.00 AC: 0 AN: 462

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5
Mutation Taster		=50/50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149847195; hg19: chr16-88780635;