3-126499367-C-T

Variant names:

Variant summary

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

The NM_144639.3(UROC1):c.1286G>A(p.Arg429His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,612,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R429C) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

UROC1
NM_144639.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.25

Publications

0 publications found

Variant links:

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

UROC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UROC1	NM_144639.3 link	c.1286G>A	p.Arg429His	missense_variant	Exon 13 of 20	ENST00000290868.7	NP_653240.1
UROC1	NM_001165974.2 link	c.1466G>A	p.Arg489His	missense_variant	Exon 14 of 21		NP_001159446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROC1	ENST00000290868.7 link	c.1286G>A	p.Arg429His	missense_variant	Exon 13 of 20	1	NM_144639.3	ENSP00000290868.2
UROC1	ENST00000383579.3 link	c.1466G>A	p.Arg489His	missense_variant	Exon 14 of 21	1		ENSP00000373073.3

Frequencies

GnomAD3 genomes

AF:

0.0000596

AC:

AN:

151062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000949

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000360

AC:

AN:

249682

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000622

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000119

AC:

174

AN:

1461102

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000147

AC:

163

AN:

1111890

Other (OTH)

AF:

0.000132

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000595

AC:

AN:

151180

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73832

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

41058

American (AMR)

AF:

0.00

AC:

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4712

European-Finnish (FIN)

AF:

0.0000949

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67810

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000757

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1286G>A (p.R429H) alteration is located in exon 13 (coding exon 13) of the UROC1 gene. This alteration results from a G to A substitution at nucleotide position 1286, causing the arginine (R) at amino acid position 429 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

not provided

Uncertain:1

Nov 02, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.85

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.2

M;.

PhyloP100

3.2

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.24

Sift

Benign

0.057

T;D

Sift4G

Benign

0.13

T;T

Vest4

0.67

ClinPred

0.93

GERP RS

4.9

Varity_R

0.31

gMVP

0.72

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over