rs1555971008

chrX-38352582-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5 BP4

The NM_001407092.1(OTC):c.-79-36C>T variant causes a intron change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: OTC NM_001407092.1 intron
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.99

Genes affected

OTC (HGNC:8512): (ornithine transcarbamylase) This nuclear gene encodes a mitochondrial matrix enzyme. The encoded protein is involved in the urea cycle which functions to detoxify ammonia into urea for excretion. Mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP5: Variant X-38352582-C-T is Pathogenic according to our data. Variant chrX-38352582-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 487344.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTC	NM_001407092.1	c.-79-36C>T		intron_variant
OTC	NM_000531.6			upstream_gene_variant		ENST00000039007.5
OTC	XM_017029556.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTC	ENST00000039007.5			upstream_gene_variant		1	NM_000531.6	P1
OTC	ENST00000488812.1			upstream_gene_variant		5
OTC	ENST00000643344.1			upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ornithine carbamoyltransferase deficiency Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Caldovic Lab, Children's National Health System

Dec 12, 2017

The patient had clinical and biochemical symptoms of OTC deficiency, and no disease causing sequence variants in the OTC coding sequence and canonical splice sites. Functional testing in cultured cells indicates reduced expression of reporter gene. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
Cadd	Benign	21
Dann	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1555971008; hg19: chrX-38211835;