19-51099038-C-A

Variant names:

• chr19-51099038-C-A
• rs770771525
• NM_145232.4:c.610G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145232.4(CTU1):​c.610G>T​(p.Gly204Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000728 in 1,511,402 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: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CTU1 NM_145232.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39399824).

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.610G>T	p.Gly204Trp	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.610G>T	p.Gly204Trp	missense	Exon 3 of 3	ENSP00000390011.1	Q7Z7A3
	CTU1	ENST00000936078.1		c.610G>T	p.Gly204Trp	missense	Exon 3 of 3	ENSP00000606137.1
	CTU1	ENST00000951779.1		c.610G>T	p.Gly204Trp	missense	Exon 3 of 3	ENSP00000621838.1

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151692 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000221 AC: 3 AN: 1359710 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 672424

African (AFR) AF: 0.00 AC: 0 AN: 29006

American (AMR) AF: 0.0000297 AC: 1 AN: 33690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23670

East Asian (EAS) AF: 0.00 AC: 0 AN: 33652

South Asian (SAS) AF: 0.00 AC: 0 AN: 78278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1066110

Other (OTH) AF: 0.00 AC: 0 AN: 56094

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151692 Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4 AN XY: 74102

African (AFR) AF: 0.0000483 AC: 2 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67864

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000295 AC: 3

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.83	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.46		Loss of disorder (P = 0.0012)
MVP		0.48
MPC		2.4
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.75
gMVP		0.72
Mutation Taster		=68/32	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: rs770771525; hg19: chr19-51602295; COSMIC: COSV101361847;