Genetic Variant UPRT:p.Ser72Phe (chrX-75274469-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_145052.4(UPRT):c.215C>T(p.Ser72Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000642 in 1,209,768 control chromosomes in the GnomAD database, including 1 homozygotes. There are 269 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., 13 hem., cov: 23)

Exomes 𝑓: 0.00066 ( 1 hom. 256 hem. )

Consequence

UPRT
NM_145052.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.0900

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054303706).

BP6

Variant X-75274469-C-T is Benign according to our data. Variant chrX-75274469-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1206381.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000665 (730/1097877) while in subpopulation MID AF = 0.0215 (89/4132). AF 95% confidence interval is 0.0179. There are 1 homozygotes in GnomAdExome4. There are 256 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 13 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UPRT	NM_145052.4	MANE Select	c.215C>T	p.Ser72Phe	missense	Exon 1 of 7	NP_659489.1	Q96BW1-1
UPRT	NM_001307944.1		c.215C>T	p.Ser72Phe	missense	Exon 1 of 7	NP_001294873.1	A0A0A0MRR5
UPRT	NM_001363821.1		c.-22-19003C>T		intron	N/A	NP_001350750.1	E9PSD7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UPRT	ENST00000373383.9	TSL:1 MANE Select	c.215C>T	p.Ser72Phe	missense	Exon 1 of 7	ENSP00000362481.4	Q96BW1-1
UPRT	ENST00000462237.5	TSL:1	n.215C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000433987.1	Q96BW1-2
UPRT	ENST00000531704.5	TSL:1	n.385C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.000438

AC:

AN:

111840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000284

Gnomad ASJ

AF:

0.00302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0210

Gnomad NFE

AF:

0.000489

Gnomad OTH

AF:

0.00266

GnomAD2 exomes

AF:

0.000691

AC:

125

AN:

180895

AF XY:

0.000727

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000745

Gnomad OTH exome

AF:

0.00203

GnomAD4 exome

AF:

0.000665

AC:

730

AN:

1097877

Hom.:

Cov.:

AF XY:

0.000705

AC XY:

256

AN XY:

363283

show subpopulations

African (AFR)

AF:

0.000492

AC:

AN:

26401

American (AMR)

AF:

0.000654

AC:

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

106

AN:

19376

East Asian (EAS)

AF:

0.00

AC:

AN:

30191

South Asian (SAS)

AF:

0.000240

AC:

AN:

54089

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40436

Middle Eastern (MID)

AF:

0.0215

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.000475

AC:

400

AN:

842030

Other (OTH)

AF:

0.00187

AC:

AN:

46056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000420

AC:

AN:

111891

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

AN XY:

34061

show subpopulations

African (AFR)

AF:

0.0000973

AC:

AN:

30820

American (AMR)

AF:

0.000283

AC:

AN:

10587

Ashkenazi Jewish (ASJ)

AF:

0.00302

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3511

South Asian (SAS)

AF:

0.00

AC:

AN:

2645

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6098

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000489

AC:

AN:

53158

Other (OTH)

AF:

0.00263

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000909

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000892

AC:

ExAC

AF:

0.000519

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.18

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.75

M_CAP

Benign

0.0087

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.090

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

REVEL

Benign

0.067

Sift

Uncertain

0.010

Sift4G

Uncertain

0.035

Polyphen

0.019

Vest4

0.16

MVP

0.043

MPC

0.19

ClinPred

0.024

GERP RS

-2.2

PromoterAI

-0.052

Neutral

(source)

Varity_R

0.061

gMVP

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over