chrX-38352582-C-T

Position:

• chrX-38352582-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000465127.1(ENSG00000250349):​c.172-313539C>T variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 3.99

Genes affected

ENSG00000250349 (HGNC:):

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTC	NM_001407092.1	c.-79-36C>T		intron_variant			NP_001394021.1
OTC	NM_000531.6	c.-115C>T		upstream_gene_variant		ENST00000039007.5	NP_000522.3
OTC	XM_017029556.2	c.-115C>T		upstream_gene_variant			XP_016885045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1	c.172-313539C>T		intron_variant		5		ENSP00000417050.1
OTC	ENST00000039007.5	c.-115C>T		upstream_gene_variant		1	NM_000531.6	ENSP00000039007.4
OTC	ENST00000488812.1	n.-23C>T		upstream_gene_variant		5
OTC	ENST00000643344.1	n.-115C>T		upstream_gene_variant				ENSP00000496606.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ornithine carbamoyltransferase deficiency Pathogenic:1 Uncertain:1

Uncertain significance, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	May 31, 2023	- -
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;