3-124737895-G-C

Position:

chr3-124737895-G-C

Variant summary

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

The NM_000373.4(UMPS):c.638G>C(p.Gly213Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,970 control chromosomes in the GnomAD database, including 27,370 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2589 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24781 hom. )

Consequence

UMPS
NM_000373.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 2.92

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017309785).

BP6

Variant 3-124737895-G-C is Benign according to our data. Variant chr3-124737895-G-C is described in ClinVar as [Benign]. Clinvar id is 100127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 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.638G>C	p.Gly213Ala	missense_variant	3/6	ENST00000232607.7	NP_000364.1
UMPS	NR_033434.2 linkuse as main transcript	n.504G>C		non_coding_transcript_exon_variant	2/5
UMPS	NR_033437.2 linkuse as main transcript	n.757G>C		non_coding_transcript_exon_variant	4/7
UMPS	XR_001740253.3 linkuse as main transcript	n.658G>C		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMPS	ENST00000232607.7 linkuse as main transcript	c.638G>C	p.Gly213Ala	missense_variant	3/6	1	NM_000373.4	ENSP00000232607	P1	P11172-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27042

AN:

152052

Hom.:

2584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.194

AC:

48772

AN:

251114

Hom.:

5295

AF XY:

0.191

AC XY:

25888

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.0997

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.181

AC:

264528

AN:

1461800

Hom.:

24781

Cov.:

AF XY:

0.181

AC XY:

131544

AN XY:

727198

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:

0.215

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.178

AC:

27068

AN:

152170

Hom.:

2589

Cov.:

AF XY:

0.181

AC XY:

13451

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.0988

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.168

Hom.:

1647

Bravo

AF:

0.180

TwinsUK

AF:

0.179

AC:

662

ALSPAC

AF:

0.176

AC:

678

ESP6500AA

AF:

0.155

AC:

681

ESP6500EA

AF:

0.171

AC:

1470

ExAC

AF:

0.189

AC:

22909

Asia WGS

AF:

0.191

AC:

666

AN:

3478

EpiCase

AF:

0.171

EpiControl

AF:

0.163

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	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. -

not provided

Benign:1Other:1

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.18

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.0077

P;P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.63

REVEL

Benign

0.13

Sift

Benign

0.46

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.099

MPC

0.23

ClinPred

0.026

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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