chrX-38351716-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000465127.1(ENSG00000250349):​c.172-314405A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000906 in 110,403 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 0.0000091 (0 hom., 0 hem., cov: 23)
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTC	NM_001407092.1	c.-79-902A>C		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>C		intron_variant	Intron 3 of 8	5		ENSP00000417050.1
OTC	ENST00000713758.1	c.-79-902A>C		intron_variant	Intron 2 of 11			ENSP00000519059.1
OTC	ENST00000713759.1	c.-88-15575A>C		intron_variant	Intron 1 of 9			ENSP00000519060.1
OTC	ENST00000713760.1	n.-79-902A>C		intron_variant	Intron 2 of 12			ENSP00000519061.1

Frequencies

GnomAD3 genomes AF: 0.00000906 AC: 1 AN: 110403 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000906 AC: 1 AN: 110403 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 32591

African (AFR) AF: 0.00 AC: 0 AN: 30291

American (AMR) AF: 0.00 AC: 0 AN: 10377

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2623

East Asian (EAS) AF: 0.00 AC: 0 AN: 3497

South Asian (SAS) AF: 0.00 AC: 0 AN: 2599

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52781

Other (OTH) AF: 0.00 AC: 0 AN: 1482

Alfa AF: 0.00 Hom.: 9447

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.47
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;