rs5963411

Variant names:

• chrX-38351864-G-A
• rs5963411
• ENST00000465127.1:c.172-314257G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-38351864-G-A
• chrX-38351864-G-C

Variant summary

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

The ENST00000465127.1(ENSG00000250349):​c.172-314257G>A 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 (19518 hom., 22899 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903
• Publications: 3 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=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_001407092.1	c.-79-754G>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.172-314257G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
OTC	ENST00000713758.1	c.-79-754G>A		intron_variant	Intron 2 of 11			ENSP00000519059.1
OTC	ENST00000713759.1	c.-88-15427G>A		intron_variant	Intron 1 of 9			ENSP00000519060.1
OTC	ENST00000713760.1	n.-79-754G>A		intron_variant	Intron 2 of 12			ENSP00000519061.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 77750 AN: 110147 Hom.: 19524 Cov.: 23

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.718

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: 0.706 AC: 77786 AN: 110201 Hom.: 19518 Cov.: 23 AF XY: 0.701 AC XY: 22899 AN XY: 32653

African (AFR) AF: 0.687 AC: 20742 AN: 30202

American (AMR) AF: 0.694 AC: 7253 AN: 10452

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2053 AN: 2627

East Asian (EAS) AF: 0.723 AC: 2506 AN: 3465

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

European-Finnish (FIN) AF: 0.641 AC: 3733 AN: 5824

Middle Eastern (MID) AF: 0.805 AC: 173 AN: 215

European-Non Finnish (NFE) AF: 0.718 AC: 37797 AN: 52666

Other (OTH) AF: 0.683 AC: 1017 AN: 1488

Alfa AF: 0.699 Hom.: 5335

Bravo AF: 0.705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.55
PhyloP100		-0.90

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: rs5963411; hg19: chrX-38211117;