X-38352256-A-G

Variant names:

• chrX-38352256-A-G
• rs5917572
• ENST00000465127.1:c.172-313865A>G

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.172-313865A>G 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 0.70 (19599 hom., 22417 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.985
• Publications: 2 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-38352256-A-G is Benign according to our data. Variant chrX-38352256-A-G is described in ClinVar as [Benign]. Clinvar id is 516560.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.-79-362A>G		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.172-313865A>G		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
OTC	ENST00000713758.1	c.-79-362A>G		intron_variant	Intron 2 of 11			ENSP00000519059.1
OTC	ENST00000713759.1	c.-88-15035A>G		intron_variant	Intron 1 of 9			ENSP00000519060.1
OTC	ENST00000713760.1	n.-79-362A>G		intron_variant	Intron 2 of 12			ENSP00000519061.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 77430 AN: 109897 Hom.: 19605 Cov.: 22

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.682

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: 0.705 AC: 77464 AN: 109948 Hom.: 19599 Cov.: 22 AF XY: 0.695 AC XY: 22417 AN XY: 32234

African (AFR) AF: 0.685 AC: 20676 AN: 30166

American (AMR) AF: 0.692 AC: 7163 AN: 10346

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2056 AN: 2631

East Asian (EAS) AF: 0.722 AC: 2520 AN: 3491

South Asian (SAS) AF: 0.758 AC: 1976 AN: 2606

European-Finnish (FIN) AF: 0.627 AC: 3525 AN: 5626

Middle Eastern (MID) AF: 0.804 AC: 172 AN: 214

European-Non Finnish (NFE) AF: 0.718 AC: 37832 AN: 52713

Other (OTH) AF: 0.683 AC: 1010 AN: 1479

Alfa AF: 0.695 Hom.: 5956

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. -

OTC-related disorder Benign:1

Dec 01, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.74
PhyloP100		0.98
PromoterAI		0.0048	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: rs5917572; hg19: chrX-38211509;