13-27978146-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001105577.2(URAD):​c.482G>T​(p.Arg161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000261 in 1,530,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R161H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

URAD
NM_001105577.2 missense

Scores

13
3
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.65
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
URADNM_001105577.2 linkc.482G>T p.Arg161Leu missense_variant Exon 2 of 2 ENST00000332715.6 NP_001099047.1 A6NGE7
URADNR_197241.1 linkn.367G>T non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
URADENST00000332715.6 linkc.482G>T p.Arg161Leu missense_variant Exon 2 of 2 5 NM_001105577.2 ENSP00000333490.4 A6NGE7

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000218
AC:
3
AN:
1378612
Hom.:
0
Cov.:
29
AF XY:
0.00000439
AC XY:
3
AN XY:
684012
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.0000175
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.482G>T (p.R161L) 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 482, causing the arginine (R) at amino acid position 161 to be replaced by a leucine (L). 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
Uncertain
0.48
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
T
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.71
T
M_CAP
Pathogenic
0.75
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Pathogenic
4.1
H
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-7.0
D
REVEL
Pathogenic
0.87
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.84
MutPred
0.67
Gain of catalytic residue at S159 (P = 0.0033);
MVP
0.49
MPC
1.2
ClinPred
1.0
D
GERP RS
4.2
Varity_R
0.96
gMVP
0.57

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.

Other links and lift over

dbSNP: rs1167280822; hg19: chr13-28552283; API