16-88714227-GGTGT-GGTGTGTGTGGGTGTGTGT

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The NM_001012759.3(CTU2):c.1097+5_1097+6insTGTGGGTGTGTGTG variant causes a frameshift, splice region change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: CTU2 NM_001012759.3 frameshift, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54

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 Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTU2	NM_001012759.3	c.1097+5_1097+6insTGTGGGTGTGTGTG		frameshift_variant, splice_region_variant		ENST00000453996.7
CTU2	NM_001012762.3	c.1097+5_1097+6insTGTGGGTGTGTGTG		frameshift_variant, splice_region_variant
CTU2	NM_001318507.2	c.1310+5_1310+6insTGTGGGTGTGTGTG		frameshift_variant, splice_region_variant
CTU2	NM_001318513.2	c.836+5_836+6insTGTGGGTGTGTGTG		frameshift_variant, splice_region_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTU2	ENST00000453996.7	c.1097+5_1097+6insTGTGGGTGTGTGTG		frameshift_variant, splice_region_variant		1	NM_001012759.3	P2

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

GnomAD3 exomes AF: 0.0000322 AC: 8 AN: 248558 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134954

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 SAS 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

Gnomad4 AFR exome AF: 0.000807

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000182

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000222

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.000473

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149847195; hg19: chr16-88780635;