rs13146

Positions:

chr3-124743961-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000373.4(UMPS):c.1320C>T(p.Gly440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,944 control chromosomes in the GnomAD database, including 27,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2592 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24834 hom. )

Consequence

UMPS
NM_000373.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.371

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-124743961-C-T is Benign according to our data. Variant chr3-124743961-C-T is described in ClinVar as [Benign]. Clinvar id is 255958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.371 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 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.1320C>T	p.Gly440=	synonymous_variant	6/6	ENST00000232607.7	NP_000364.1
UMPS	NR_033434.2 linkuse as main transcript	n.1186C>T		non_coding_transcript_exon_variant	5/5
UMPS	NR_033437.2 linkuse as main transcript	n.1439C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMPS	ENST00000232607.7 linkuse as main transcript	c.1320C>T	p.Gly440=	synonymous_variant	6/6	1	NM_000373.4	ENSP00000232607	P1	P11172-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27064

AN:

152068

Hom.:

2587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.0992

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.194

AC:

48885

AN:

251448

Hom.:

5332

AF XY:

0.191

AC XY:

25953

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.0998

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.181

AC:

264732

AN:

1461758

Hom.:

24834

Cov.:

AF XY:

0.181

AC XY:

131672

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.178

AC:

27090

AN:

152186

Hom.:

2592

Cov.:

AF XY:

0.181

AC XY:

13459

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.0992

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.170

Hom.:

5477

Bravo

AF:

0.180

Asia WGS

AF:

0.192

AC:

668

AN:

3478

EpiCase

AF:

0.171

EpiControl

AF:

0.163

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oroticaciduria

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary orotic aciduria, type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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