Genetic Variant URAD:p.Ala91Ser (chr13-27978357-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001105577.2(URAD):c.271G>T(p.Ala91Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000454 in 1,408,266 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A91T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

URAD
NM_001105577.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

URAD (HGNC:17785): (ureidoimidazoline (2-oxo-4-hydroxy-4-carboxy-5-) decarboxylase) Predicted to enable carboxy-lyase activity. Predicted to be involved in purine-containing compound catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

URAD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
URAD	NM_001105577.2 link	c.271G>T	p.Ala91Ser	missense_variant	Exon 2 of 2	ENST00000332715.6	NP_001099047.1	A6NGE7
URAD	NR_197241.1 link	n.156G>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
URAD	ENST00000332715.6 link	c.271G>T	p.Ala91Ser	missense_variant	Exon 2 of 2	5	NM_001105577.2	ENSP00000333490.4		A6NGE7

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.0000287

AC:

AN:

34864

Hom.:

AF XY:

0.0000495

AC XY:

AN XY:

20200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000321

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1256212

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

614048

show subpopulations

Gnomad4 AFR exome

AF:

0.000641

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.0000505

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000289

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000869

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000336

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271G>T (p.A91S) alteration is located in exon 2 (coding exon 2) of the URAD gene. This alteration results from a G to T substitution at nucleotide position 271, causing the alanine (A) at amino acid position 91 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.81

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.26

Sift

Benign

0.051

Sift4G

Uncertain

0.048

Polyphen

0.53

Vest4

0.43

MutPred

0.68

Gain of glycosylation at A91 (P = 0.0071);

MVP

0.23

MPC

0.93

ClinPred

0.71

GERP RS

3.0

Varity_R

0.37

gMVP

0.089

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

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