X-38352591-C-G

Variant names:

• chrX-38352591-C-G
• rs749748052
• ENST00000465127.1:c.172-313530C>G

Variant summary

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

The NM_001407092.1(OTC):​c.-79-27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 483,418 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000041 (0 hom. 1 hem.)
• Consequence: OTC NM_001407092.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 0 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: Orphanet, Laboratory for Molecular Medicine, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

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=-0.62).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407092.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTC	NM_001407092.1		c.-79-27C>G		intron	N/A	NP_001394021.1	P00480
	OTC	NM_000531.6	MANE Select	c.-106C>G		upstream_gene	N/A	NP_000522.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-313530C>G		intron	N/A	ENSP00000417050.1	B4E171
	OTC	ENST00000909238.1		c.-106C>G		5_prime_UTR	Exon 1 of 10	ENSP00000579297.1
	OTC	ENST00000909239.1		c.-106C>G		5_prime_UTR	Exon 1 of 9	ENSP00000579298.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000414 AC: 2 AN: 483418 Hom.: 0 Cov.: 7 AF XY: 0.00000642 AC XY: 1 AN XY: 155650

African (AFR) AF: 0.00 AC: 0 AN: 14181

American (AMR) AF: 0.00 AC: 0 AN: 29392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14882

East Asian (EAS) AF: 0.00 AC: 0 AN: 24909

South Asian (SAS) AF: 0.00 AC: 0 AN: 39646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35479

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2211

European-Non Finnish (NFE) AF: 0.00000673 AC: 2 AN: 297378

Other (OTH) AF: 0.00 AC: 0 AN: 25340

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		1.0
PromoterAI		0.019	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs749748052; hg19: chrX-38211844;