ENST00000465127.1:c.172-314405A>G

Variant names:

• chrX-38351716-A-G
• rs5963409
• ENST00000465127.1:c.172-314405A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000465127.1(ENSG00000250349):​c.172-314405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (19980 hom., 22990 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 8 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465127.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTC	NM_001407092.1		c.-79-902A>G		intron	N/A	NP_001394021.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-314405A>G		intron	N/A	ENSP00000417050.1
	OTC	ENST00000713758.1		c.-79-902A>G		intron	N/A	ENSP00000519059.1
	OTC	ENST00000713759.1		c.-88-15575A>G		intron	N/A	ENSP00000519060.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 78567 AN: 110374 Hom.: 19988 Cov.: 23

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.811

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.689

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: 0.712 AC: 78600 AN: 110427 Hom.: 19980 Cov.: 23 AF XY: 0.704 AC XY: 22990 AN XY: 32639

African (AFR) AF: 0.709 AC: 21506 AN: 30347

American (AMR) AF: 0.696 AC: 7228 AN: 10388

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2048 AN: 2623

East Asian (EAS) AF: 0.725 AC: 2525 AN: 3484

South Asian (SAS) AF: 0.765 AC: 1982 AN: 2590

European-Finnish (FIN) AF: 0.635 AC: 3707 AN: 5837

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

European-Non Finnish (NFE) AF: 0.718 AC: 37863 AN: 52764

Other (OTH) AF: 0.690 AC: 1035 AN: 1501

Alfa AF: 0.665 Hom.: 9447

Bravo AF: 0.712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.90
DANN	Benign	0.51
PhyloP100		-0.38

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: rs5963409; hg19: chrX-38210969;