Variant 3-126488206-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_144639.3(UROC1):c.1782C>T(p.Gly594Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,614,064 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0028 ( 9 hom. )

Consequence

UROC1
NM_144639.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.847

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 3-126488206-G-A is Benign according to our data. Variant chr3-126488206-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 726175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UROC1	NM_144639.3 linkuse as main transcript	c.1782C>T	p.Gly594Gly	synonymous_variant	18/20	ENST00000290868.7	NP_653240.1	Q96N76-1
UROC1	NM_001165974.2 linkuse as main transcript	c.1962C>T	p.Gly654Gly	synonymous_variant	19/21		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.1782C>T	p.Gly594Gly	synonymous_variant	18/20	1	NM_144639.3	ENSP00000290868.2		Q96N76-1
UROC1	ENST00000383579.3 linkuse as main transcript	c.1962C>T	p.Gly654Gly	synonymous_variant	19/21	1		ENSP00000373073.3		Q96N76-2

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

289

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00304

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00196

AC:

493

AN:

251472

Hom.:

AF XY:

0.00213

AC XY:

289

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00276

AC:

4031

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

1990

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00230

Gnomad4 FIN exome

AF:

0.000730

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.00190

AC:

289

AN:

152208

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00304

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00183

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00308

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	UROC1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.8

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.31

Position offset: -8

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