X-75300920-C-A

Variant names:

• chrX-75300920-C-A
• NM_145052.4:c.778C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145052.4(UPRT):​c.778C>A​(p.Gln260Lys) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 22)
• Consequence: UPRT NM_145052.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

Genes affected

UPRT (HGNC:28334): (uracil phosphoribosyltransferase homolog) This gene encodes uracil phosphoribosyltransferase, which catalyzes the conversion of uracil and 5-phosphoribosyl-1-R-diphosphate to uridine monophosphate (UMP). This reaction is an important part of nucleotide metabolism, specifically the pyrimidine salvage pathway. The enzyme localizes to the nucleus and cytoplasm. The protein is a potential target for rational design of drugs to treat parasitic infections and cancer. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39724115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPRT	NM_145052.4	c.778C>A	p.Gln260Lys	missense_variant	Exon 6 of 7	ENST00000373383.9	NP_659489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPRT	ENST00000373383.9	c.778C>A	p.Gln260Lys	missense_variant	Exon 6 of 7	1	NM_145052.4	ENSP00000362481.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.778C>A (p.Q260K) alteration is located in exon 6 (coding exon 6) of the UPRT gene. This alteration results from a C to A substitution at nucleotide position 778, causing the glutamine (Q) at amino acid position 260 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T;.;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	-0.66	N;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.33	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.64	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.023	B;.;.
Vest4		0.54
MutPred		0.51		Gain of methylation at Q260 (P = 0.0038);Gain of methylation at Q260 (P = 0.0038);.;
MVP		0.62
MPC		1.9
ClinPred		0.84	D
GERP RS		5.4
Varity_R		0.37
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-74520755;