X-38352036-C-T

Variant names:

• chrX-38352036-C-T
• rs5963412
• ENST00000465127.1:c.172-314085C>T

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.172-314085C>T 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 (19549 hom., 23366 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21
• Publications: 1 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=-1.04).
• BP6: Variant X-38352036-C-T is Benign according to our data. Variant chrX-38352036-C-T is described in ClinVar as [Benign]. Clinvar id is 680700.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.-79-582C>T		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.172-314085C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
OTC	ENST00000713758.1	c.-79-582C>T		intron_variant	Intron 2 of 11			ENSP00000519059.1
OTC	ENST00000713759.1	c.-88-15255C>T		intron_variant	Intron 1 of 9			ENSP00000519060.1
OTC	ENST00000713760.1	n.-79-582C>T		intron_variant	Intron 2 of 12			ENSP00000519061.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 78276 AN: 110957 Hom.: 19555 Cov.: 24

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.683

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: 78312 AN: 111013 Hom.: 19549 Cov.: 24 AF XY: 0.700 AC XY: 23366 AN XY: 33389

African (AFR) AF: 0.687 AC: 20981 AN: 30533

American (AMR) AF: 0.694 AC: 7305 AN: 10521

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2060 AN: 2639

East Asian (EAS) AF: 0.724 AC: 2530 AN: 3493

South Asian (SAS) AF: 0.762 AC: 2034 AN: 2670

European-Finnish (FIN) AF: 0.634 AC: 3733 AN: 5884

Middle Eastern (MID) AF: 0.799 AC: 171 AN: 214

European-Non Finnish (NFE) AF: 0.717 AC: 37936 AN: 52880

Other (OTH) AF: 0.684 AC: 1031 AN: 1507

Alfa AF: 0.709 Hom.: 5695

Bravo AF: 0.705

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.33
PhyloP100		-3.2

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: rs5963412; hg19: chrX-38211289;