X-38352177-CTTCT-C

Variant names:

• chrX-38352177-CTTCT-C
• rs57752938
• ENST00000465127.1:c.172-313943_172-313940delTTCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000465127.1(ENSG00000250349):​c.172-313943_172-313940delTTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (19297 hom., 22310 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61
• 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 -2 ACMG points.

• BP6: Variant X-38352177-CTTCT-C is Benign according to our data. Variant chrX-38352177-CTTCT-C is described in ClinVar as [Benign]. Clinvar id is 1283242.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.-79-436_-79-433delTTCT		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.172-313943_172-313940delTTCT		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
OTC	ENST00000713758.1	c.-79-440_-79-437delTTCT		intron_variant	Intron 2 of 11			ENSP00000519059.1
OTC	ENST00000713759.1	c.-88-15113_-88-15110delTTCT		intron_variant	Intron 1 of 9			ENSP00000519060.1
OTC	ENST00000713760.1	n.-79-440_-79-437delTTCT		intron_variant	Intron 2 of 12			ENSP00000519061.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 76869 AN: 110043 Hom.: 19302 Cov.: 0

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.679

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: 0.699 AC: 76905 AN: 110095 Hom.: 19297 Cov.: 0 AF XY: 0.688 AC XY: 22310 AN XY: 32429

African (AFR) AF: 0.668 AC: 20172 AN: 30193

American (AMR) AF: 0.689 AC: 7141 AN: 10370

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2061 AN: 2636

East Asian (EAS) AF: 0.720 AC: 2498 AN: 3469

South Asian (SAS) AF: 0.753 AC: 1960 AN: 2603

European-Finnish (FIN) AF: 0.628 AC: 3593 AN: 5725

Middle Eastern (MID) AF: 0.800 AC: 172 AN: 215

European-Non Finnish (NFE) AF: 0.716 AC: 37761 AN: 52714

Other (OTH) AF: 0.679 AC: 1015 AN: 1494

Alfa AF: 0.706 Hom.: 5660

Bravo AF: 0.699

Asia WGS AF: 0.765 AC: 1926 AN: 2522

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

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: rs57752938; hg19: chrX-38211430;