rs954349089

Variant names:

• chr16-88706579-C-A
• rs954349089
• NM_001012759.3:c.49C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-88706579-C-A
• chr16-88706579-C-G
• chr16-88706579-C-T

Variant summary

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

The NM_001012759.3(CTU2):​c.49C>A​(p.Pro17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CTU2 NM_001012759.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• 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=0.105288684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.49C>A	p.Pro17Thr	missense_variant	Exon 1 of 15	ENST00000453996.7	NP_001012777.1
RNF166	NM_178841.4	c.-254G>T		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.49C>A	p.Pro17Thr	missense_variant	Exon 1 of 15	1	NM_001012759.3	ENSP00000388320.2
RNF166	ENST00000312838.9	c.-254G>T		upstream_gene_variant		1	NM_178841.4	ENSP00000326095.4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 33

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.70e-7 AC: 1 AN: 1299112 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 640666

African (AFR) AF: 0.00 AC: 0 AN: 25822

American (AMR) AF: 0.00 AC: 0 AN: 22006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22476

East Asian (EAS) AF: 0.00 AC: 0 AN: 28150

South Asian (SAS) AF: 0.00 AC: 0 AN: 70234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3848

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1040414

Other (OTH) AF: 0.00 AC: 0 AN: 53700

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74212

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67922

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.61
DEOGEN2	Benign	0.029	T;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00016	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;.
PhyloP100		-0.34
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.13	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.79	P;P;.
Vest4		0.12
MutPred		0.27		Gain of phosphorylation at P17 (P = 0.0019);Gain of phosphorylation at P17 (P = 0.0019);Gain of phosphorylation at P17 (P = 0.0019);
MVP		0.17
ClinPred		0.34	T
GERP RS		2.1
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.054
gMVP		0.40

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: rs954349089; hg19: chr16-88772987;