Variant 3-126517680-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_144639.3(UROC1):c.40C>T(p.Arg14Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,599,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

UROC1
NM_144639.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: -0.105

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012254477).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UROC1	NM_144639.3 linkuse as main transcript	c.40C>T	p.Arg14Trp	missense_variant	1/20	ENST00000290868.7	NP_653240.1	Q96N76-1
UROC1	NM_001165974.2 linkuse as main transcript	c.40C>T	p.Arg14Trp	missense_variant	1/21		NP_001159446.1	Q96N76-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UROC1	ENST00000290868.7 linkuse as main transcript	c.40C>T	p.Arg14Trp	missense_variant	1/20	1	NM_144639.3	ENSP00000290868.2		Q96N76-1
UROC1	ENST00000383579.3 linkuse as main transcript	c.40C>T	p.Arg14Trp	missense_variant	1/21	1		ENSP00000373073.3		Q96N76-2

Frequencies

GnomAD3 genomes

AF:

0.000953

AC:

145

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00105

AC:

231

AN:

219108

Hom.:

AF XY:

0.00110

AC XY:

131

AN XY:

119380

show subpopulations

Gnomad AFR exome

AF:

0.000227

Gnomad AMR exome

AF:

0.000760

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000310

Gnomad SAS exome

AF:

0.000677

Gnomad FIN exome

AF:

0.000369

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.00201

GnomAD4 exome

AF:

0.00163

AC:

2353

AN:

1447556

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1170

AN XY:

719070

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000726

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000668

Gnomad4 SAS exome

AF:

0.000687

Gnomad4 FIN exome

AF:

0.000390

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.000837

GnomAD4 genome

AF:

0.000952

AC:

145

AN:

152326

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000901

Hom.:

Bravo

AF:

0.000914

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	UROC1: PM2, PM3:Supporting, BP4 -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 04, 2014

- -

Urocanate hydratase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.084

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.035

Sift

Benign

0.034

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.0020

B;.

Vest4

0.19

MVP

0.44

MPC

0.16

ClinPred

0.023

GERP RS

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.064

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over