19-51099034-C-G

Variant names:

• chr19-51099034-C-G
• rs773312410
• NM_145232.4:c.614G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145232.4(CTU1):​c.614G>C​(p.Gly205Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,357,398 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. G205D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CTU1 NM_145232.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.084322065).

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.614G>C	p.Gly205Ala	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.614G>C	p.Gly205Ala	missense	Exon 3 of 3	ENSP00000390011.1	Q7Z7A3
	CTU1	ENST00000936078.1		c.614G>C	p.Gly205Ala	missense	Exon 3 of 3	ENSP00000606137.1
	CTU1	ENST00000951779.1		c.614G>C	p.Gly205Ala	missense	Exon 3 of 3	ENSP00000621838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000105 AC: 13 AN: 123632 AF XY: 0.0000436

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000118 AC: 16 AN: 1357398 Hom.: 0 Cov.: 31 AF XY: 0.00000745 AC XY: 5 AN XY: 671304

African (AFR) AF: 0.00 AC: 0 AN: 28890

American (AMR) AF: 0.000476 AC: 16 AN: 33602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23558

East Asian (EAS) AF: 0.00 AC: 0 AN: 33366

South Asian (SAS) AF: 0.00 AC: 0 AN: 78138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064742

Other (OTH) AF: 0.00 AC: 0 AN: 55974

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000197 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.083	T
Sift4G	Benign	0.34	T
Polyphen		0.0060	B
Vest4		0.049
MutPred		0.39		Loss of catalytic residue at P201 (P = 0.074)
MVP		0.16
MPC		1.9
ClinPred		0.12	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.32
gMVP		0.63
Mutation Taster		=72/28	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: rs773312410; hg19: chr19-51602291;