rs987108325

Variant names:

• chr19-51098627-C-A
• rs987108325
• NM_145232.4:c.1021G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51098627-C-A
• chr19-51098627-C-T

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.1021G>T​(p.Ala341Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000173 in 1,155,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. A341T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CTU1 NM_145232.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• 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=0.04220444).

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.1021G>T	p.Ala341Ser	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.1021G>T	p.Ala341Ser	missense	Exon 3 of 3	ENSP00000390011.1	Q7Z7A3
	CTU1	ENST00000936078.1		c.1021G>T	p.Ala341Ser	missense	Exon 3 of 3	ENSP00000606137.1
	CTU1	ENST00000951779.1		c.1021G>T	p.Ala341Ser	missense	Exon 3 of 3	ENSP00000621838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000173 AC: 2 AN: 1155800 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 556304

African (AFR) AF: 0.00 AC: 0 AN: 23180

American (AMR) AF: 0.00 AC: 0 AN: 8758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15778

East Asian (EAS) AF: 0.00 AC: 0 AN: 26534

South Asian (SAS) AF: 0.00 AC: 0 AN: 44288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 0.00000208 AC: 2 AN: 959370

Other (OTH) AF: 0.00 AC: 0 AN: 46568

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.088
DANN	Benign	0.55
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.87
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.011
Sift	Benign	0.65	T
Sift4G	Benign	0.46	T
Polyphen		0.0070	B
Vest4		0.073
MutPred		0.11		Gain of phosphorylation at A341 (P = 0.0034)
MVP		0.030
MPC		0.95
ClinPred		0.028	T
GERP RS		-3.6
Varity_R		0.044
gMVP		0.37
Mutation Taster		=98/2	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: rs987108325; hg19: chr19-51601884;