rs3772810

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000460034.5(UMPS):n.*1215A>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 0.0155 in 1,612,548 control chromosomes in the GnomAD database, including 362 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 36 hom., cov: 32)

Exomes 𝑓: 0.016 ( 326 hom. )

Consequence

UMPS
ENST00000460034.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.108

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

orotic aciduria
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

UMPS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UMPS	NM_000373.4 link	c.*28A>G	3_prime_UTR_variant	Exon 6 of 6	ENST00000232607.7	NP_000364.1	P11172-1A8K5J1
UMPS	NR_033434.2 link	n.1337A>G	non_coding_transcript_exon_variant	Exon 5 of 5
UMPS	NR_033437.2 link	n.1590A>G	non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMPS	ENST00000232607.7 link	c.*28A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_000373.4	ENSP00000232607.2		P11172-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2053

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0557

Gnomad SAS

AF:

0.0458

Gnomad FIN

AF:

0.00633

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0226

AC:

5671

AN:

251170

AF XY:

0.0228

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.0409

Gnomad ASJ exome

AF:

0.00864

Gnomad EAS exome

AF:

0.0617

Gnomad FIN exome

AF:

0.00705

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0158

AC:

23007

AN:

1460466

Hom.:

326

Cov.:

AF XY:

0.0164

AC XY:

11881

AN XY:

726602

show subpopulations

African (AFR)

AF:

0.00260

AC:

AN:

33446

American (AMR)

AF:

0.0414

AC:

1850

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00804

AC:

210

AN:

26104

East Asian (EAS)

AF:

0.0616

AC:

2443

AN:

39660

South Asian (SAS)

AF:

0.0408

AC:

3511

AN:

86130

European-Finnish (FIN)

AF:

0.00715

AC:

381

AN:

53270

Middle Eastern (MID)

AF:

0.00538

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0122

AC:

13514

AN:

1111076

Other (OTH)

AF:

0.0162

AC:

980

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1364

2728

4093

5457

6821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0136

AC:

2066

AN:

152082

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1077

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00371

AC:

154

AN:

41550

American (AMR)

AF:

0.0294

AC:

448

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3472

East Asian (EAS)

AF:

0.0559

AC:

289

AN:

5174

South Asian (SAS)

AF:

0.0461

AC:

220

AN:

4774

European-Finnish (FIN)

AF:

0.00633

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

824

AN:

67962

Other (OTH)

AF:

0.0114

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

101

201

302

402

503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oroticaciduria

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary orotic aciduria, type 1

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.3

(source)

DANN

Benign

0.77

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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rs3772810

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over