chr19-51098816-C-T

Variant names:

• chr19-51098816-C-T
• rs920483360
• NM_145232.4:c.832G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05591765).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU1	NM_145232.4	MANE Select	c.832G>A	p.Ala278Thr	missense	Exon 3 of 3	NP_660275.2	Q7Z7A3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTU1	ENST00000421832.3	TSL:2 MANE Select	c.832G>A	p.Ala278Thr	missense	Exon 3 of 3	ENSP00000390011.1	Q7Z7A3
	CTU1	ENST00000936078.1		c.832G>A	p.Ala278Thr	missense	Exon 3 of 3	ENSP00000606137.1
	CTU1	ENST00000951779.1		c.832G>A	p.Ala278Thr	missense	Exon 3 of 3	ENSP00000621838.1

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

African (AFR) AF: 0.00 AC: 0 AN: 17376

American (AMR) AF: 0.00 AC: 0 AN: 3396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7538

East Asian (EAS) AF: 0.00 AC: 0 AN: 10840

South Asian (SAS) AF: 0.00 AC: 0 AN: 18840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11900

Middle Eastern (MID) AF: 0.000485 AC: 1 AN: 2062

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 818546

Other (OTH) AF: 0.00 AC: 0 AN: 32518

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.9
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
Mutation Taster		=95/5	polymorphism

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: rs920483360; hg19: chr19-51602073;