3-124735327-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000373.4(UMPS):c.310+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,298,672 control chromosomes in the GnomAD database, including 45,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4455 hom., cov: 33)
  • Exomes 𝑓: 0.26 (40596 hom.)
• Consequence: UMPS NM_000373.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.586

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-124735327-A-G is Benign according to our data. Variant chr3-124735327-A-G is described in ClinVar as [Benign]. Clinvar id is 1249492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMPS	NM_000373.4	c.310+81A>G		intron_variant		ENST00000232607.7
UMPS	NR_033434.2	n.177-2241A>G		intron_variant, non_coding_transcript_variant
UMPS	NR_033437.2	n.429+81A>G		intron_variant, non_coding_transcript_variant
UMPS	XR_001740253.3	n.330+81A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMPS	ENST00000232607.7	c.310+81A>G		intron_variant		1	NM_000373.4	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34483 AN: 152030 Hom.: 4460 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.259 AC: 296951 AN: 1146524 Hom.: 40596 AF XY: 0.258 AC XY: 148684 AN XY: 577300

Gnomad4 AFR exome AF: 0.0992

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.227 AC: 34473 AN: 152148 Hom.: 4455 Cov.: 33 AF XY: 0.226 AC XY: 16808 AN XY: 74366

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.269

Alfa AF: 0.278 Hom.: 5849

Bravo AF: 0.231

Asia WGS AF: 0.258 AC: 894 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	10
Dann	Benign	0.85

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

Other links and lift over

dbSNP: rs3772804; hg19: chr3-124454174; COSMIC: COSV51739561; COSMIC: COSV51739561;