13-27978369-C-T

Variant names:

• chr13-27978369-C-T
• NM_001105577.2:c.259G>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.259G>A​(p.Glu87Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000799 in 1,251,080 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: URAD NM_001105577.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• 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, 0.923

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.259G>A	p.Glu87Lys	missense	Exon 2 of 2	NP_001099047.1	A6NGE7
	URAD	NR_197241.1		n.144G>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.259G>A	p.Glu87Lys	missense	Exon 2 of 2	ENSP00000333490.4	A6NGE7
	URAD	ENST00000713555.1		n.250G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.99e-7 AC: 1 AN: 1251080 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 611400

African (AFR) AF: 0.00 AC: 0 AN: 24842

American (AMR) AF: 0.0000621 AC: 1 AN: 16092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19620

East Asian (EAS) AF: 0.00 AC: 0 AN: 27404

South Asian (SAS) AF: 0.00 AC: 0 AN: 59242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3986

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1017308

Other (OTH) AF: 0.00 AC: 0 AN: 51702

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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		2.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.77		Gain of MoRF binding (P = 0.0056)
MVP		0.44
MPC		1.1
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.97
gMVP		0.36
Mutation Taster		=86/14	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: chr13-28552506;