13-27978333-C-G

Variant names:

• chr13-27978333-C-G
• NM_001105577.2:c.295G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105577.2(URAD):​c.295G>C​(p.Asp99His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000805 in 1,242,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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: 1.38

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13285032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
URAD	NM_001105577.2	c.295G>C	p.Asp99His	missense_variant	Exon 2 of 2	ENST00000332715.6	NP_001099047.1
URAD	NR_197241.1	n.180G>C		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.295G>C	p.Asp99His	missense_variant	Exon 2 of 2	5	NM_001105577.2	ENSP00000333490.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.05e-7 AC: 1 AN: 1242844 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 605888

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: 0.00

Gnomad4 OTH exome AF: 0.0000195

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.295G>C (p.D99H) alteration is located in exon 2 (coding exon 2) of the URAD gene. This alteration results from a G to C substitution at nucleotide position 295, causing the aspartic acid (D) at amino acid position 99 to be replaced by a histidine (H). 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	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Benign	0.087	T
Sift4G	Benign	0.080	T
Polyphen		0.057	B
Vest4		0.079
MutPred		0.48		Gain of MoRF binding (P = 0.0494);
MVP		0.13
MPC		0.43
ClinPred		0.13	T
GERP RS		1.9
Varity_R		0.16
gMVP		0.16

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: chr13-28552470;