16-88714227-GGTGT-GGTGTGTGTGGGTGTGTGTGGGTGTGTGT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001012759.3(CTU2):​c.1097+5_1097+6insTGTGGGTGTGTGTGGGTGTGTGTG 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 0.000024 (0 hom., cov: 0)
• 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: Uncertain_significance. The variant received 0 ACMG points.

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+6insTGTGGGTGTGTGTGGGTGTGTGTG		splice_region intron	N/A	NP_001012777.1
	CTU2	NM_001318507.2		c.1310+5_1310+6insTGTGGGTGTGTGTGGGTGTGTGTG		splice_region intron	N/A	NP_001305436.1
	CTU2	NM_001012762.3		c.1097+5_1097+6insTGTGGGTGTGTGTGGGTGTGTGTG		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+1insGTGTGTGTGGGTGTGTGTGGGTGT		splice_donor intron	N/A	ENSP00000388320.2
	CTU2	ENST00000567949.5	TSL:1	c.1310_1310+1insGTGTGTGTGGGTGTGTGTGGGTGT		splice_donor intron	N/A	ENSP00000456908.1
	CTU2	ENST00000564105.5	TSL:1	n.*808_*808+1insGTGTGTGTGGGTGTGTGTGGGTGT		splice_donor intron	N/A	ENSP00000454923.1

Frequencies

GnomAD3 genomes AF: 0.0000237 AC: 1 AN: 42254 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000237 AC: 1 AN: 42254 Hom.: 0 Cov.: 0 AF XY: 0.0000499 AC XY: 1 AN XY: 20030

African (AFR) AF: 0.00 AC: 0 AN: 16802

American (AMR) AF: 0.00 AC: 0 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: 0.000321 AC: 1 AN: 3112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

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

Other (OTH) AF: 0.00 AC: 0 AN: 460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5
Mutation Taster		=51/49	polymorphism

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;