19-51098816-C-T

Position:

• chr19-51098816-C-T

Variant summary

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

The NM_145232.4(CTU1):​c.832G>A​(p.Ala278Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000108 in 923,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: CTU1 NM_145232.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

Genes affected

CTU1 (HGNC:29590): (cytosolic thiouridylase subunit 1) Predicted to enable tRNA binding activity. Predicted to be involved in tRNA wobble position uridine thiolation. Predicted to be located in cytosol. Predicted to be part of cytosolic tRNA wobble base thiouridylase complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.05591765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTU1	NM_145232.4	c.832G>A	p.Ala278Thr	missense_variant	3/3	ENST00000421832.3	NP_660275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTU1	ENST00000421832.3	c.832G>A	p.Ala278Thr	missense_variant	3/3	2	NM_145232.4	ENSP00000390011	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000108 AC: 1 AN: 923016 Hom.: 0 Cov.: 29 AF XY: 0.00000231 AC XY: 1 AN XY: 433668

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 03, 2024

The c.832G>A (p.A278T) alteration is located in exon 3 (coding exon 2) of the CTU1 gene. This alteration results from a G to A substitution at nucleotide position 832, causing the alanine (A) at amino acid position 278 to be replaced by a threonine (T). 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	0.087
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.080	N
REVEL	Benign	0.014
Sift	Benign	0.74	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.19		Gain of glycosylation at A278 (P = 0.0035);
MVP		0.030
MPC		1.0
ClinPred		0.077	T
GERP RS		-4.8
Varity_R		0.027
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

Publications

LitVar

Other links and lift over

dbSNP: rs920483360; hg19: chr19-51602073;