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. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate

The ENST00000453996.7(CTU2):​c.1097_1097+1insGTGTGTGTGGGTGTGTGTGGGTGT variant causes a splice donor, intron change. 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 ENST00000453996.7 splice_donor, intron
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.059431523 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7, offset of 0 (no position change), new splice context is: cagGTgtgt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.1097+5_1097+6insTGTGGGTGTGTGTGGGTGTGTGTG		splice_region_variant, intron_variant	Intron 10 of 14	ENST00000453996.7	NP_001012777.1
CTU2	NM_001318507.2	c.1310+5_1310+6insTGTGGGTGTGTGTGGGTGTGTGTG		splice_region_variant, intron_variant	Intron 10 of 14		NP_001305436.1
CTU2	NM_001012762.3	c.1097+5_1097+6insTGTGGGTGTGTGTGGGTGTGTGTG		splice_region_variant, intron_variant	Intron 10 of 13		NP_001012780.1
CTU2	NM_001318513.2	c.836+5_836+6insTGTGGGTGTGTGTGGGTGTGTGTG		splice_region_variant, intron_variant	Intron 9 of 13		NP_001305442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7	c.1097_1097+1insGTGTGTGTGGGTGTGTGTGGGTGT		splice_donor_variant, intron_variant	Intron 10 of 14	1	NM_001012759.3	ENSP00000388320.2

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000321

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;