chr3-124740091-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000373.4(UMPS):c.1050T>A(p.Val350Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,614,088 control chromosomes in the GnomAD database, including 489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 37 hom., cov: 32)

Exomes 𝑓: 0.017 ( 452 hom. )

Consequence

UMPS
NM_000373.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.736

Publications

13 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-124740091-T-A is Benign according to our data. Variant chr3-124740091-T-A is described in ClinVar as Benign. ClinVar VariationId is 100129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.736 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMPS	NM_000373.4 link	c.1050T>A	p.Val350Val	synonymous_variant	Exon 4 of 6	ENST00000232607.7	NP_000364.1	P11172-1A8K5J1
UMPS	NR_033434.2 link	n.916T>A		non_coding_transcript_exon_variant	Exon 3 of 5
UMPS	NR_033437.2 link	n.1169T>A		non_coding_transcript_exon_variant	Exon 5 of 7
UMPS	XR_001740253.3 link	n.1274T>A		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMPS	ENST00000232607.7 link	c.1050T>A	p.Val350Val	synonymous_variant	Exon 4 of 6	1	NM_000373.4	ENSP00000232607.2		P11172-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2124

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0291

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0627

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.00623

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0245

AC:

6149

AN:

251454

AF XY:

0.0253

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.0415

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.0691

Gnomad FIN exome

AF:

0.00702

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0169

AC:

24727

AN:

1461876

Hom.:

452

Cov.:

AF XY:

0.0178

AC XY:

12954

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

33480

American (AMR)

AF:

0.0420

AC:

1880

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00803

AC:

210

AN:

26136

East Asian (EAS)

AF:

0.0780

AC:

3098

AN:

39700

South Asian (SAS)

AF:

0.0517

AC:

4459

AN:

86256

European-Finnish (FIN)

AF:

0.00713

AC:

381

AN:

53420

Middle Eastern (MID)

AF:

0.00538

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0122

AC:

13555

AN:

1112002

Other (OTH)

AF:

0.0172

AC:

1039

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1403

2806

4209

5612

7015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.0140

AC:

2135

AN:

152212

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1119

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00356

AC:

148

AN:

41536

American (AMR)

AF:

0.0296

AC:

453

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3472

East Asian (EAS)

AF:

0.0629

AC:

326

AN:

5186

South Asian (SAS)

AF:

0.0530

AC:

255

AN:

4810

European-Finnish (FIN)

AF:

0.00623

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

822

AN:

68006

Other (OTH)

AF:

0.0118

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

104

208

311

415

519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0115

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.0490

AC:

169

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Diasio Lab, Mayo Clinic

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Oroticaciduria

Benign:1

Jan 12, 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. -

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

-0.45

CADD

Benign

1.7

(source)

DANN

Benign

0.73

PhyloP100

-0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over