16-88707186-T-C

Variant names:

• chr16-88707186-T-C
• rs61730430
• NM_001012759.3:c.119T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001012759.3(CTU2):​c.119T>C​(p.Ile40Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 6.70

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.119T>C	p.Ile40Thr	missense_variant	Exon 2 of 15	ENST00000453996.7	NP_001012777.1
CTU2	NM_001318507.2	c.119T>C	p.Ile40Thr	missense_variant	Exon 2 of 15		NP_001305436.1
CTU2	NM_001012762.3	c.119T>C	p.Ile40Thr	missense_variant	Exon 2 of 14		NP_001012780.1
CTU2	NM_001318513.2	c.-64T>C		5_prime_UTR_variant	Exon 2 of 14		NP_001305442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTU2	ENST00000453996.7	c.119T>C	p.Ile40Thr	missense_variant	Exon 2 of 15	1	NM_001012759.3	ENSP00000388320.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.8	M;M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.81
MutPred		0.69		Loss of stability (P = 0.015);Loss of stability (P = 0.015);Loss of stability (P = 0.015);
MVP		0.55
ClinPred		0.98	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.43
gMVP		0.53

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: rs61730430; hg19: chr16-88773594;