X-38351716-A-G

Variant names:

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

Variant summary

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

The NM_001407092.1(OTC):​c.-79-902A>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: OTC NM_001407092.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_001407092.1	c.-79-902A>G		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.172-314405A>G		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 78567 AN: 110374 Hom.: 19988 Cov.: 23 AF XY: 0.704 AC XY: 22946 AN XY: 32576

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

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.690

Alfa AF: 0.530 Hom.: 2068

Bravo AF: 0.712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs5963409; hg19: chrX-38210969;