ENST00000465127.1:c.172-313783G>A

Variant names:

• chrX-38352338-G-A
• rs5917573
• ENST00000465127.1:c.172-313783G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000465127.1(ENSG00000250349):​c.172-313783G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (19605 hom., 22860 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0100
• Publications: 5 publications found

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]

OTC Gene-Disease associations (from GenCC):

• ornithine carbamoyltransferase deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-38352338-G-A is Benign according to our data. Variant chrX-38352338-G-A is described in ClinVar as [Benign]. Clinvar id is 516401.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_001407092.1	c.-79-280G>A		intron_variant	Intron 2 of 11		NP_001394021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1	c.172-313783G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 77882 AN: 110321 Hom.: 19611 Cov.: 23

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.811

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.706 AC: 77919 AN: 110374 Hom.: 19605 Cov.: 23 AF XY: 0.700 AC XY: 22860 AN XY: 32644

African (AFR) AF: 0.687 AC: 20813 AN: 30288

American (AMR) AF: 0.694 AC: 7195 AN: 10373

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2064 AN: 2639

East Asian (EAS) AF: 0.727 AC: 2544 AN: 3497

South Asian (SAS) AF: 0.764 AC: 2017 AN: 2639

European-Finnish (FIN) AF: 0.630 AC: 3585 AN: 5689

Middle Eastern (MID) AF: 0.802 AC: 174 AN: 217

European-Non Finnish (NFE) AF: 0.718 AC: 37970 AN: 52861

Other (OTH) AF: 0.685 AC: 1022 AN: 1492

Alfa AF: 0.705 Hom.: 7302

Bravo AF: 0.705

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Ornithine carbamoyltransferase deficiency Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.70
PhyloP100		0.010
PromoterAI		-0.00090	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs5917573; hg19: chrX-38211591;