19-51098707-C-A

Variant names:

• chr19-51098707-C-A
• rs1339692634
• NM_145232.4:c.941G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145232.4(CTU1):​c.941G>T​(p.Arg314Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R314H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTU1 NM_145232.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23459327).

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.941G>T	p.Arg314Leu	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.941G>T	p.Arg314Leu	missense	Exon 3 of 3	ENSP00000390011.1	Q7Z7A3
	CTU1	ENST00000936078.1		c.941G>T	p.Arg314Leu	missense	Exon 3 of 3	ENSP00000606137.1
	CTU1	ENST00000951779.1		c.941G>T	p.Arg314Leu	missense	Exon 3 of 3	ENSP00000621838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.96e-7 AC: 1 AN: 1115512 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 536390

African (AFR) AF: 0.0000455 AC: 1 AN: 21996

American (AMR) AF: 0.00 AC: 0 AN: 8434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14324

East Asian (EAS) AF: 0.00 AC: 0 AN: 23746

South Asian (SAS) AF: 0.00 AC: 0 AN: 41182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 933674

Other (OTH) AF: 0.00 AC: 0 AN: 43740

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.59	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.14
Sift	Benign	0.059	T
Sift4G	Uncertain	0.010	D
Polyphen		0.96	P
Vest4		0.23
MutPred		0.43		Loss of methylation at R314 (P = 0.0087)
MVP		0.37
MPC		1.3
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.27
gMVP		0.53
Mutation Taster		=65/35	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: rs1339692634; hg19: chr19-51601964;