X-75274636-G-C

Variant names:

• chrX-75274636-G-C
• rs771975802
• NM_145052.4:c.382G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145052.4(UPRT):​c.382G>C​(p.Asp128His) variant causes a missense change. The variant allele was found at a frequency of 0.000000928 in 1,077,668 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic 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. D128N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: UPRT NM_145052.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.46
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145052.4. 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
	UPRT	NM_145052.4	MANE Select	c.382G>C	p.Asp128His	missense	Exon 1 of 7	NP_659489.1	Q96BW1-1
	UPRT	NM_001307944.1		c.382G>C	p.Asp128His	missense	Exon 1 of 7	NP_001294873.1	A0A0A0MRR5
	UPRT	NM_001363821.1		c.-22-18836G>C		intron	N/A	NP_001350750.1	E9PSD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPRT	ENST00000373383.9	TSL:1 MANE Select	c.382G>C	p.Asp128His	missense	Exon 1 of 7	ENSP00000362481.4	Q96BW1-1
	UPRT	ENST00000462237.5	TSL:1	n.382G>C		non_coding_transcript_exon	Exon 1 of 8	ENSP00000433987.1	Q96BW1-2
	UPRT	ENST00000531704.5	TSL:1	n.552G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.28e-7 AC: 1 AN: 1077668 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 347422

African (AFR) AF: 0.0000384 AC: 1 AN: 26069

American (AMR) AF: 0.00 AC: 0 AN: 33351

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18167

East Asian (EAS) AF: 0.00 AC: 0 AN: 29841

South Asian (SAS) AF: 0.00 AC: 0 AN: 50682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4026

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 830598

Other (OTH) AF: 0.00 AC: 0 AN: 45190

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.64
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		5.5
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.53		Gain of MoRF binding (P = 0.0397)
MVP		1.0
MPC		2.8
ClinPred		1.0	D
GERP RS		5.1
PromoterAI		0.051	Neutral
Varity_R		0.93
gMVP		0.95
Mutation Taster		=20/80	disease causing

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: rs771975802; hg19: chrX-74494471;