16-88707191-G-A

Variant names:

• chr16-88707191-G-A
• rs1339742213
• NM_001012759.3:c.124G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001012759.3(CTU2):​c.124G>A​(p.Ala42Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CTU2 NM_001012759.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.56

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38946337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTU2	NM_001012759.3	c.124G>A	p.Ala42Thr	missense_variant	Exon 2 of 15	ENST00000453996.7	NP_001012777.1
CTU2	NM_001318507.2	c.124G>A	p.Ala42Thr	missense_variant	Exon 2 of 15		NP_001305436.1
CTU2	NM_001012762.3	c.124G>A	p.Ala42Thr	missense_variant	Exon 2 of 14		NP_001012780.1
CTU2	NM_001318513.2	c.-59G>A		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.124G>A	p.Ala42Thr	missense_variant	Exon 2 of 15	1	NM_001012759.3	ENSP00000388320.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461596 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727072

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 09, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0028	T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		1.0	D;P;.
Vest4		0.49
MutPred		0.63		Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);
MVP		0.54
ClinPred		0.97	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1339742213; hg19: chr16-88773599;