X-75303443-A-G

Variant names:

• chrX-75303443-A-G
• rs776349931
• NM_145052.4:c.862A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145052.4(UPRT):​c.862A>G​(p.Ile288Val) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000037 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: UPRT NM_145052.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33825555).

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.862A>G	p.Ile288Val	missense	Exon 7 of 7	NP_659489.1	Q96BW1-1
	UPRT	NM_001363821.1		c.454A>G	p.Ile152Val	missense	Exon 10 of 10	NP_001350750.1	E9PSD7
	UPRT	NM_001307944.1		c.*66A>G		3_prime_UTR	Exon 7 of 7	NP_001294873.1	A0A0A0MRR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPRT	ENST00000373383.9	TSL:1 MANE Select	c.862A>G	p.Ile288Val	missense	Exon 7 of 7	ENSP00000362481.4	Q96BW1-1
	UPRT	ENST00000462237.5	TSL:1	n.*389A>G		non_coding_transcript_exon	Exon 8 of 8	ENSP00000433987.1	Q96BW1-2
	UPRT	ENST00000462237.5	TSL:1	n.*389A>G		3_prime_UTR	Exon 8 of 8	ENSP00000433987.1	Q96BW1-2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000112 AC: 2 AN: 178512 AF XY: 0.0000158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000384

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000365 AC: 4 AN: 1094756 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 1 AN XY: 360950

African (AFR) AF: 0.00 AC: 0 AN: 26282

American (AMR) AF: 0.0000289 AC: 1 AN: 34652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19335

East Asian (EAS) AF: 0.00 AC: 0 AN: 29986

South Asian (SAS) AF: 0.00 AC: 0 AN: 53490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40499

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3526

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 841078

Other (OTH) AF: 0.00 AC: 0 AN: 45908

GnomAD4 genome Cov.: 22

Alfa AF: 0.000111 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	0.73	N
PhyloP100		7.3
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.47	N
REVEL	Uncertain	0.45
Sift	Benign	0.28	T
Sift4G	Benign	0.24	T
Polyphen		0.22	B
Vest4		0.58
MutPred		0.53		Gain of loop (P = 0.2045)
MVP		0.55
MPC		1.5
ClinPred		0.51	D
GERP RS		5.2
Varity_R		0.22
gMVP		0.85
Mutation Taster		=88/12	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: rs776349931; hg19: chrX-74523278;