rs3772810

Variant names:

• chr3-124744112-A-G
• rs3772810
• ENST00000460034.5:n.*1215A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (36 hom., cov: 32)
  • Exomes 𝑓: 0.016 (326 hom.)
• Consequence: UMPS ENST00000460034.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.108
• Publications: 14 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-124744112-A-G is Benign according to our data. Variant chr3-124744112-A-G is described in ClinVar as Benign. ClinVar VariationId is 342937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000460034.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMPS	NM_000373.4	MANE Select	c.*28A>G		3_prime_UTR	Exon 6 of 6	NP_000364.1
	UMPS	NR_033434.2		n.1337A>G		non_coding_transcript_exon	Exon 5 of 5
	UMPS	NR_033437.2		n.1590A>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMPS	ENST00000460034.5	TSL:1	n.*1215A>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000420409.1
	UMPS	ENST00000462091.5	TSL:1	n.*1143A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000417893.1
	UMPS	ENST00000467167.5	TSL:1	n.*1369A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000419618.1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2053 AN: 151964 Hom.: 35 Cov.: 32

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

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.: 32 AF XY: 0.0164 AC XY: 11881 AN XY: 726602

African (AFR) AF: 0.00260 AC: 87 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: 31 AN: 5762

European-Non Finnish (NFE) AF: 0.0122 AC: 13514 AN: 1111076

Other (OTH) AF: 0.0162 AC: 980 AN: 60326

GnomAD4 genome AF: 0.0136 AC: 2066 AN: 152082 Hom.: 36 Cov.: 32 AF XY: 0.0145 AC XY: 1077 AN XY: 74342

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: 39 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: 67 AN: 10584

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0121 AC: 824 AN: 67962

Other (OTH) AF: 0.0114 AC: 24 AN: 2108

Alfa AF: 0.0135 Hom.: 61

Bravo AF: 0.0140

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary orotic aciduria, type 1 (1)
-	-	1	not provided (1)
-	-	1	Oroticaciduria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.3
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)

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

Other links and lift over

dbSNP: rs3772810; hg19: chr3-124462959; COSMIC: COSV51737949; COSMIC: COSV51737949;