3-124740091-T-A

Position:

chr3-124740091-T-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000232607.7(UMPS):c.1050T>A(p.Val350=) 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
ENST00000232607.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.736

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein
UMPS	NM_000373.4 linkuse as main transcript	c.1050T>A	p.Val350=	synonymous_variant	4/6	ENST00000232607.7	NP_000364.1
UMPS	NR_033434.2 linkuse as main transcript	n.916T>A		non_coding_transcript_exon_variant	3/5
UMPS	NR_033437.2 linkuse as main transcript	n.1169T>A		non_coding_transcript_exon_variant	5/7
UMPS	XR_001740253.3 linkuse as main transcript	n.1274T>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMPS	ENST00000232607.7 linkuse as main transcript	c.1050T>A	p.Val350=	synonymous_variant	4/6	1	NM_000373.4	ENSP00000232607	P1	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

GnomAD3 exomes

AF:

0.0245

AC:

6149

AN:

251454

Hom.:

164

AF XY:

0.0253

AC XY:

3436

AN XY:

135898

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 SAS exome

AF:

0.0530

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

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.0420

Gnomad4 ASJ exome

AF:

0.00803

Gnomad4 EAS exome

AF:

0.0780

Gnomad4 SAS exome

AF:

0.0517

Gnomad4 FIN exome

AF:

0.00713

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0140

AC:

2135

AN:

152212

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1119

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00356

Gnomad4 AMR

AF:

0.0296

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.0629

Gnomad4 SAS

AF:

0.0530

Gnomad4 FIN

AF:

0.00623

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.0118

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	Diasio Lab, Mayo Clinic	-	- -

Oroticaciduria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

1.7

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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