13-27978330-C-G

Variant names:

• chr13-27978330-C-G
• rs1354727253
• NM_001105577.2:c.298G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001105577.2(URAD):​c.298G>C​(p.Glu100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E100K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: URAD NM_001105577.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105577.2. 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
	URAD	NM_001105577.2	MANE Select	c.298G>C	p.Glu100Gln	missense	Exon 2 of 2	NP_001099047.1	A6NGE7
	URAD	NR_197241.1		n.183G>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URAD	ENST00000332715.6	TSL:5 MANE Select	c.298G>C	p.Glu100Gln	missense	Exon 2 of 2	ENSP00000333490.4	A6NGE7
	URAD	ENST00000713555.1		n.289G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.60	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.21
Sift	Benign	0.13	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.66	P
Vest4		0.16
MutPred		0.74		Gain of MoRF binding (P = 0.0216)
MVP		0.22
MPC		0.77
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.43
gMVP		0.24
Mutation Taster		=89/11	polymorphism

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: rs1354727253; hg19: chr13-28552467;