3-126488206-G-T

Variant names:

• chr3-126488206-G-T
• rs139120643
• NM_144639.3:c.1782C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144639.3(UROC1):​c.1782C>A​(p.Gly594Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G594G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: UROC1 NM_144639.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 3 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, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.847 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROC1	NM_144639.3	MANE Select	c.1782C>A	p.Gly594Gly	synonymous	Exon 18 of 20	NP_653240.1	Q96N76-1
	UROC1	NM_001165974.2		c.1962C>A	p.Gly654Gly	synonymous	Exon 19 of 21	NP_001159446.1	Q96N76-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROC1	ENST00000290868.7	TSL:1 MANE Select	c.1782C>A	p.Gly594Gly	synonymous	Exon 18 of 20	ENSP00000290868.2	Q96N76-1
	UROC1	ENST00000383579.3	TSL:1	c.1962C>A	p.Gly654Gly	synonymous	Exon 19 of 21	ENSP00000373073.3	Q96N76-2
	UROC1	ENST00000875183.1		c.1854C>A	p.Gly618Gly	synonymous	Exon 19 of 21	ENSP00000545242.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.82
DANN	Benign	0.73
PhyloP100		-0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs139120643; hg19: chr3-126207049;