X-75274469-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 1206381.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chrX-75274469-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 256 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPRT	NM_145052.4 link	c.215C>T	p.Ser72Phe	missense_variant	Exon 1 of 7	ENST00000373383.9	NP_659489.1	Q96BW1-1A8KAF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPRT	ENST00000373383.9 link	c.215C>T	p.Ser72Phe	missense_variant	Exon 1 of 7	1	NM_145052.4	ENSP00000362481.4		Q96BW1-1

Frequencies

GnomAD3 genomes

AF:

0.000438

AC:

AN:

111840

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

AN XY:

34000

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

GnomAD3 exomes

AF:

0.000691

AC:

125

AN:

180895

Hom.:

AF XY:

0.000727

AC XY:

AN XY:

66047

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 SAS exome

AF:

0.000159

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

Gnomad4 AFR exome

AF:

0.000492

Gnomad4 AMR exome

AF:

0.000654

Gnomad4 ASJ exome

AF:

0.00547

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000475

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.000420

AC:

AN:

111891

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

AN XY:

34061

show subpopulations

Gnomad4 AFR

AF:

0.0000973

Gnomad4 AMR

AF:

0.000283

Gnomad4 ASJ

AF:

0.00302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000489

Gnomad4 OTH

AF:

0.00263

Alfa

AF:

0.000968

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000892

AC:

ExAC

AF:

0.000519

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Uncertain:1

Aug 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215C>T (p.S72F) alteration is located in exon 1 (coding exon 1) of the UPRT gene. This alteration results from a C to T substitution at nucleotide position 215, causing the serine (S) at amino acid position 72 to be replaced by a phenylalanine (F). 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

0.085

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.18

T;.

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.067

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

0.019

B;.

Vest4

0.16

MVP

0.043

MPC

0.19

ClinPred

0.024

GERP RS

-2.2

Varity_R

0.061

gMVP

0.23

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