Variant X-75274453-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145052.4(UPRT):c.199G>A(p.Gly67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000512 in 1,209,859 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000049 ( 0 hom. 20 hem. )

Consequence

UPRT
NM_145052.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.403

Variant links:

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]

UPRT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05350882).

BS2

High Hemizygotes in GnomAdExome4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPRT	NM_145052.4 link	c.199G>A	p.Gly67Arg	missense_variant	1/7	ENST00000373383.9	NP_659489.1	Q96BW1-1A8KAF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPRT	ENST00000373383.9 link	c.199G>A	p.Gly67Arg	missense_variant	1/7	1	NM_145052.4	ENSP00000362481.4		Q96BW1-1

Frequencies

GnomAD3 genomes

AF:

0.0000715

AC:

AN:

111961

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34115

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000938

AC:

AN:

181213

Hom.:

AF XY:

0.000136

AC XY:

AN XY:

66143

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.000448

GnomAD4 exome

AF:

0.0000492

AC:

AN:

1097898

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

363276

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000570

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000715

AC:

AN:

111961

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34115

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.199G>A (p.G67R) alteration is located in exon 1 (coding exon 1) of the UPRT gene. This alteration results from a G to A substitution at nucleotide position 199, causing the glycine (G) at amino acid position 67 to be replaced by an arginine (R). 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

0.070

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.1

DANN

Benign

0.73

DEOGEN2

Benign

0.15

T;.

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.029

Sift

Benign

0.37

T;T

Sift4G

Uncertain

0.052

T;D

Polyphen

0.0

B;.

Vest4

0.11

MutPred

0.15

Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);

MVP

0.068

MPC

0.19

ClinPred

0.019

GERP RS

1.3

Varity_R

0.051

gMVP

0.33

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over