X-38351864-G-A

Position:

• chrX-38351864-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001407092.1(OTC):​c.-79-754G>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: OTC NM_001407092.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTC	NM_001407092.1	c.-79-754G>A		intron_variant			NP_001394021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1	c.172-314257G>A		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 77750 AN: 110147 Hom.: 19524 Cov.: 23 AF XY: 0.701 AC XY: 22854 AN XY: 32589

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

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.683

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs5963411; hg19: chrX-38211117;