16-88706555-G-T

Variant names:

• chr16-88706555-G-T
• rs137933845
• NM_001012759.3:c.25G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318513.2(CTU2):​c.-158G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000765 in 1,306,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CTU2 NM_001318513.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• 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]

RNF166 (HGNC:28856): (ring finger protein 166) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10452199).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318513.2. 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.25G>T	p.Gly9Trp	missense	Exon 1 of 15	NP_001012777.1	Q2VPK5-1
	CTU2	NM_001318513.2		c.-158G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001305442.1	Q2VPK5-3
	CTU2	NM_001318507.2		c.25G>T	p.Gly9Trp	missense	Exon 1 of 15	NP_001305436.1	H3BSW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU2	ENST00000453996.7	TSL:1 MANE Select	c.25G>T	p.Gly9Trp	missense	Exon 1 of 15	ENSP00000388320.2	Q2VPK5-1
	CTU2	ENST00000567949.5	TSL:1	c.25G>T	p.Gly9Trp	missense	Exon 1 of 15	ENSP00000456908.1	H3BSW6
	CTU2	ENST00000564105.5	TSL:1	n.25G>T		non_coding_transcript_exon	Exon 1 of 14	ENSP00000454923.1	H3BNM3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.65e-7 AC: 1 AN: 1306566 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 644522

African (AFR) AF: 0.00 AC: 0 AN: 26132

American (AMR) AF: 0.00 AC: 0 AN: 23248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22794

East Asian (EAS) AF: 0.00 AC: 0 AN: 28144

South Asian (SAS) AF: 0.00 AC: 0 AN: 71358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3926

European-Non Finnish (NFE) AF: 9.58e-7 AC: 1 AN: 1044230

Other (OTH) AF: 0.00 AC: 0 AN: 54044

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.00016	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.79
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.14	T
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.11
MutPred		0.11		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.44
ClinPred		0.68	D
GERP RS		1.1
PromoterAI		-0.0023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.088
gMVP		0.27
Mutation Taster		=95/5	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: rs137933845; hg19: chr16-88772963;