3-126488206-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_144639.3(UROC1):c.1782C>T(p.Gly594=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.847

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]

ACMG classification

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 GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UROC1	NM_144639.3	c.1782C>T	p.Gly594=	synonymous_variant	18/20	ENST00000290868.7
UROC1	NM_001165974.2	c.1962C>T	p.Gly654=	synonymous_variant	19/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROC1	ENST00000290868.7	c.1782C>T	p.Gly594=	synonymous_variant	18/20	1	NM_144639.3	P1
UROC1	ENST00000383579.3	c.1962C>T	p.Gly654=	synonymous_variant	19/21	1

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 152090 Hom.: 1 Cov.: 34

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.: 3 AF XY: 0.00213 AC XY: 289 AN XY: 135908

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.: 9 Cov.: 32 AF XY: 0.00274 AC XY: 1990 AN XY: 727226

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.: 1 Cov.: 34 AF XY: 0.00179 AC XY: 133 AN XY: 74428

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.: 0

Bravo AF: 0.00183

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00305

EpiControl AF: 0.00308

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2021	- -

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

Other links and lift over

dbSNP: rs139120643; hg19: chr3-126207049; COSMIC: COSV52035663;