chr16-88706552-T-G

Variant names:

• chr16-88706552-T-G
• rs1471557333
• NM_001012759.3:c.22T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012759.3(CTU2):​c.22T>G​(p.Tyr8Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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)
• Consequence: CTU2 NM_001012759.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12475869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.22T>G	p.Tyr8Asp	missense_variant	Exon 1 of 15	ENST00000453996.7	NP_001012777.1
RNF166	NM_178841.4	c.-227A>C		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.22T>G	p.Tyr8Asp	missense_variant	Exon 1 of 15	1	NM_001012759.3	ENSP00000388320.2
RNF166	ENST00000312838.9	c.-227A>C		upstream_gene_variant		1	NM_178841.4	ENSP00000326095.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.0083	T;.;.
Eigen	Benign	0.17
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.5	D;D;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.91	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.21
MutPred		0.25		Loss of phosphorylation at Y8 (P = 0);Loss of phosphorylation at Y8 (P = 0);Loss of phosphorylation at Y8 (P = 0);
MVP		0.39
ClinPred		0.86	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs1471557333; hg19: chr16-88772960;