rs759533169

Variant names:

• chr13-27978257-C-A
• NM_001105577.2:c.371G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-27978257-C-A
• chr13-27978257-C-G
• chr13-27978257-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001105577.2(URAD):​c.371G>T​(p.Arg124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000233 in 1,289,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R124H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: URAD NM_001105577.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
URAD	NM_001105577.2	c.371G>T	p.Arg124Leu	missense_variant	Exon 2 of 2	ENST00000332715.6	NP_001099047.1
URAD	NR_197241.1	n.256G>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	c.371G>T	p.Arg124Leu	missense_variant	Exon 2 of 2	5	NM_001105577.2	ENSP00000333490.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000233 AC: 3 AN: 1289744 Hom.: 0 Cov.: 29 AF XY: 0.00000158 AC XY: 1 AN XY: 633360

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: 0.00000289

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.28
Sift	Benign	0.034	D
Sift4G	Uncertain	0.036	D
Polyphen		0.37	B
Vest4		0.46
MutPred		0.73		Gain of catalytic residue at F119 (P = 0.0025);
MVP		0.37
MPC		0.47
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.77
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-28552394;