Variant rs1139538 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000462091.5(UMPS):n.-28A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,612,770 control chromosomes in the GnomAD database, including 277,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23578 hom., cov: 32)

Exomes 𝑓: 0.59 ( 253971 hom. )

Consequence

UMPS
ENST00000462091.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -1.35

Variant links:

Genes affected

UMPS (HGNC:12563): (uridine monophosphate synthetase) This gene encodes a uridine 5'-monophosphate synthase. The encoded protein is a bifunctional enzyme that catalyzes the final two steps of the de novo pyrimidine biosynthetic pathway. The first reaction is carried out by the N-terminal enzyme orotate phosphoribosyltransferase which converts orotic acid to orotidine-5'-monophosphate. The terminal reaction is carried out by the C-terminal enzyme OMP decarboxylase which converts orotidine-5'-monophosphate to uridine monophosphate. Defects in this gene are the cause of hereditary orotic aciduria. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

UMPS links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-124730444-A-G is Benign according to our data. Variant chr3-124730444-A-G is described in ClinVar as [Benign]. Clinvar id is 100126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMPS	NM_000373.4 linkuse as main transcript	c.-28A>G		upstream_gene_variant		ENST00000232607.7	NP_000364.1	P11172-1A8K5J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMPS	ENST00000232607.7 linkuse as main transcript	c.-28A>G		upstream_gene_variant		1	NM_000373.4	ENSP00000232607.2		P11172-1

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83484

AN:

151940

Hom.:

23564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.659

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.589

Gnomad OTH

AF:

0.589

GnomAD3 exomes

AF:

0.606

AC:

152139

AN:

251240

Hom.:

46846

AF XY:

0.606

AC XY:

82289

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.739

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.682

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.530

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.588

AC:

858625

AN:

1460710

Hom.:

253971

Cov.:

AF XY:

0.589

AC XY:

427604

AN XY:

726566

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.730

Gnomad4 ASJ exome

AF:

0.608

Gnomad4 EAS exome

AF:

0.633

Gnomad4 SAS exome

AF:

0.612

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.586

Gnomad4 OTH exome

AF:

0.586

GnomAD4 genome

AF:

0.549

AC:

83539

AN:

152060

Hom.:

23578

Cov.:

AF XY:

0.552

AC XY:

41034

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.670

Gnomad4 ASJ

AF:

0.609

Gnomad4 EAS

AF:

0.658

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.521

Gnomad4 NFE

AF:

0.589

Gnomad4 OTH

AF:

0.589

Alfa

AF:

0.585

Hom.:

12618

Bravo

AF:

0.556

Asia WGS

AF:

0.626

AC:

2179

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	Diasio Lab, Mayo Clinic	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Oroticaciduria

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.13

DANN

Benign

0.38

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