19-51099038-C-G

Variant names:

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

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>C​(p.Gly204Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,511,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G204W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CTU1 NM_145232.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.3210696).

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>C	p.Gly204Arg	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>C	p.Gly204Arg	missense	Exon 3 of 3	ENSP00000390011.1	Q7Z7A3
	CTU1	ENST00000936078.1		c.610G>C	p.Gly204Arg	missense	Exon 3 of 3	ENSP00000606137.1
	CTU1	ENST00000951779.1		c.610G>C	p.Gly204Arg	missense	Exon 3 of 3	ENSP00000621838.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151692 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

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: 0.0000442

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000161 AC: 2 AN: 124498 AF XY: 0.0000144

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000408

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000191 AC: 26 AN: 1359708 Hom.: 0 Cov.: 31 AF XY: 0.0000238 AC XY: 16 AN XY: 672422

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

American (AMR) AF: 0.00 AC: 0 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: 0.0000128 AC: 1 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: 0.0000206 AC: 22 AN: 1066108

Other (OTH) AF: 0.0000535 AC: 3 AN: 56094

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151692 Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3 AN XY: 74102

African (AFR) AF: 0.00 AC: 0 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: 0.0000442 AC: 3 AN: 67864

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.24
MutPred		0.33		Gain of solvent accessibility (P = 0.0037)
MVP		0.42
MPC		2.3
ClinPred		0.89	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.59
gMVP		0.73
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;