16-88706570-G-C

Variant names:

• chr16-88706570-G-C
• rs1217267671
• NM_001012759.3:c.40G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012759.3(CTU2):​c.40G>C​(p.Glu14Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 1,305,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: CTU2 NM_001012759.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05027613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.40G>C	p.Glu14Gln	missense_variant	Exon 1 of 15	ENST00000453996.7	NP_001012777.1
RNF166	NM_178841.4	c.-245C>G		upstream_gene_variant		ENST00000312838.9	NP_849163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7	c.40G>C	p.Glu14Gln	missense_variant	Exon 1 of 15	1	NM_001012759.3	ENSP00000388320.2
RNF166	ENST00000312838.9	c.-245C>G		upstream_gene_variant		1	NM_178841.4	ENSP00000326095.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000690 AC: 9 AN: 1305156 Hom.: 0 Cov.: 31 AF XY: 0.00000777 AC XY: 5 AN XY: 643696

African (AFR) AF: 0.00 AC: 0 AN: 26036

American (AMR) AF: 0.00 AC: 0 AN: 22842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22732

East Asian (EAS) AF: 0.00 AC: 0 AN: 28184

South Asian (SAS) AF: 0.00 AC: 0 AN: 71116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3888

European-Non Finnish (NFE) AF: 0.00000862 AC: 9 AN: 1043722

Other (OTH) AF: 0.00 AC: 0 AN: 53972

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.40G>C (p.E14Q) alteration is located in exon 1 (coding exon 1) of the CTU2 gene. This alteration results from a G to C substitution at nucleotide position 40, causing the glutamic acid (E) at amino acid position 14 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.86
DANN	Benign	0.59
DEOGEN2	Benign	0.0075	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.000030	N
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.89	L;L;.
PhyloP100		-1.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.54	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.45	P;B;.
Vest4		0.089
MutPred		0.083		Loss of glycosylation at P13 (P = 0.0775);Loss of glycosylation at P13 (P = 0.0775);Loss of glycosylation at P13 (P = 0.0775);
MVP		0.040
ClinPred		0.088	T
GERP RS		-4.4
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.076
gMVP		0.33
Mutation Taster		=96/4	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

Publications

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Other links and lift over

dbSNP: rs1217267671; hg19: chr16-88772978;