16-88707144-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012759.3(CTU2):c.77A>G(p.Gln26Arg) 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. 14/20 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)
• Consequence: CTU2 NM_001012759.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.718

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048207223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTU2	NM_001012759.3	c.77A>G	p.Gln26Arg	missense_variant	2/15	ENST00000453996.7
CTU2	NM_001318507.2	c.77A>G	p.Gln26Arg	missense_variant	2/15
CTU2	NM_001012762.3	c.77A>G	p.Gln26Arg	missense_variant	2/14
CTU2	NM_001318513.2	c.-106A>G		5_prime_UTR_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTU2	ENST00000453996.7	c.77A>G	p.Gln26Arg	missense_variant	2/15	1	NM_001012759.3	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.77A>G (p.Q26R) alteration is located in exon 2 (coding exon 2) of the CTU2 gene. This alteration results from a A to G substitution at nucleotide position 77, causing the glutamine (Q) at amino acid position 26 to be replaced by an arginine (R). 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	0.075
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	9.5
Dann	Benign	0.69
DEOGEN2	Benign	0.0016	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L;L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.41	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.81	T;T;T
Sift4G	Benign	0.69	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.14
MutPred		0.22		Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);
MVP		0.12
ClinPred		0.030	T
GERP RS		-0.95
Varity_R		0.023
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88773552;