ENST00000683807.1:n.18A>G

Variant names:

• chr3-124730405-T-C
• rs2279199
• ENST00000683807.1:n.18A>G

Variant summary

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

The ENST00000683807.1(ENSG00000288713):​n.18A>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 0.461 in 1,597,468 control chromosomes in the GnomAD database, including 171,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15447 hom., cov: 33)
  • Exomes 𝑓: 0.46 (156059 hom.)
• Consequence: ENSG00000288713 ENST00000683807.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 0.0250
• Publications: 27 publications found

Genes affected

ENSG00000288713 (HGNC:):

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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-124730405-T-C is Benign according to our data. Variant chr3-124730405-T-C is described in ClinVar as Benign. ClinVar VariationId is 100125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000683807.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMPS	NM_000373.4	MANE Select	c.-67T>C		upstream_gene	N/A	NP_000364.1	A8K5J1
	UMPS	NR_033434.2		n.-47T>C		upstream_gene	N/A
	UMPS	NR_033437.2		n.-47T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000288713	ENST00000683807.1		n.18A>G		non_coding_transcript_exon	Exon 1 of 3
	UMPS	ENST00000232607.7	TSL:1 MANE Select	c.-67T>C		upstream_gene	N/A	ENSP00000232607.2	P11172-1
	UMPS	ENST00000460034.5	TSL:1	n.-67T>C		upstream_gene	N/A	ENSP00000420409.1	F2Z303

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67687 AN: 151870 Hom.: 15439 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.470

GnomAD2 exomes AF: 0.497 AC: 119695 AN: 240742 AF XY: 0.491

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.655

Gnomad ASJ exome AF: 0.522

Gnomad EAS exome AF: 0.610

Gnomad FIN exome AF: 0.456

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.462 AC: 668105 AN: 1445480 Hom.: 156059 Cov.: 29 AF XY: 0.461 AC XY: 331350 AN XY: 718548

African (AFR) AF: 0.357 AC: 11877 AN: 33228

American (AMR) AF: 0.642 AC: 28508 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13274 AN: 25790

East Asian (EAS) AF: 0.567 AC: 22399 AN: 39518

South Asian (SAS) AF: 0.440 AC: 37528 AN: 85258

European-Finnish (FIN) AF: 0.432 AC: 21972 AN: 50846

Middle Eastern (MID) AF: 0.482 AC: 2068 AN: 4292

European-Non Finnish (NFE) AF: 0.456 AC: 502868 AN: 1102398

Other (OTH) AF: 0.462 AC: 27611 AN: 59718

GnomAD4 genome AF: 0.446 AC: 67735 AN: 151988 Hom.: 15447 Cov.: 33 AF XY: 0.448 AC XY: 33273 AN XY: 74296

African (AFR) AF: 0.365 AC: 15136 AN: 41426

American (AMR) AF: 0.555 AC: 8491 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3007 AN: 5160

South Asian (SAS) AF: 0.437 AC: 2100 AN: 4802

European-Finnish (FIN) AF: 0.426 AC: 4498 AN: 10564

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31228 AN: 67962

Other (OTH) AF: 0.471 AC: 995 AN: 2112

Alfa AF: 0.467 Hom.: 3721

Bravo AF: 0.456

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)
-	-	1	Oroticaciduria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.55
PhyloP100		0.025
PromoterAI		-0.032	Neutral
Mutation Taster		=300/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2279199;

hg19: chr3-124449252;

COSMIC: COSV51736861;

COSMIC: COSV51736861;