rs1799388

Variant names:

• chr3-126506304-T-C
• rs1799388
• NM_144639.3:c.603-293A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-126506304-T-C
• chr3-126506304-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144639.3(UROC1):​c.603-293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,162 control chromosomes in the GnomAD database, including 60,688 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60688 hom., cov: 31)
• Consequence: UROC1 NM_144639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 2 publications found

Genes affected

UROC1 (HGNC:26444): (urocanate hydratase 1) This gene encodes an enzyme involved in the second step of histidine catabolism, metabolizing urocanic acid to formiminoglutamic acid. Deficiency of this enzyme results in urocanic aciduria, and is an apparent cause of mental retardation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2021]

UROC1 Gene-Disease associations (from GenCC):

• urocanic aciduria

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROC1	NM_144639.3	MANE Select	c.603-293A>G		intron	N/A	NP_653240.1
	UROC1	NM_001165974.2		c.603-293A>G		intron	N/A	NP_001159446.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROC1	ENST00000290868.7	TSL:1 MANE Select	c.603-293A>G		intron	N/A	ENSP00000290868.2
	UROC1	ENST00000383579.3	TSL:1	c.603-293A>G		intron	N/A	ENSP00000373073.3

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135409 AN: 152044 Hom.: 60656 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.890 AC: 135495 AN: 152162 Hom.: 60688 Cov.: 31 AF XY: 0.894 AC XY: 66528 AN XY: 74392

African (AFR) AF: 0.775 AC: 32118 AN: 41466

American (AMR) AF: 0.935 AC: 14297 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3139 AN: 3468

East Asian (EAS) AF: 0.949 AC: 4908 AN: 5170

South Asian (SAS) AF: 0.924 AC: 4461 AN: 4828

European-Finnish (FIN) AF: 0.938 AC: 9943 AN: 10604

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.935 AC: 63595 AN: 68012

Other (OTH) AF: 0.899 AC: 1900 AN: 2114

Alfa AF: 0.921 Hom.: 270345

Bravo AF: 0.885

Asia WGS AF: 0.900 AC: 3131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.25
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs1799388; hg19: chr3-126225147;