chr13-27978281-C-T

Variant names:

• chr13-27978281-C-T
• NM_001105577.2:c.347G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001105577.2(URAD):​c.347G>A​(p.Gly116Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: URAD NM_001105577.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

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.347G>A	p.Gly116Asp	missense	Exon 2 of 2	NP_001099047.1	A6NGE7
	URAD	NR_197241.1		n.232G>A		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.347G>A	p.Gly116Asp	missense	Exon 2 of 2	ENSP00000333490.4	A6NGE7
	URAD	ENST00000713555.1		n.338G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.3
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Pathogenic	0.68
Sift	Benign	0.11	T
Sift4G	Benign	0.072	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.75		Gain of catalytic residue at F119 (P = 0.0288)
MVP		0.47
MPC		1.1
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.69
gMVP		0.17
Mutation Taster		=76/24	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

hg19: chr13-28552418;