ENST00000465127.1:c.172-313790A>G

Variant names:

• chrX-38352331-A-G
• rs191615506
• ENST00000465127.1:c.172-313790A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000465127.1(ENSG00000250349):​c.172-313790A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 111,999 control chromosomes in the GnomAD database, including 1 homozygotes. There are 94 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.0034 (1 hom., 94 hem., cov: 24)
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.09
• Publications: 1 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-38352331-A-G is Benign according to our data. Variant chrX-38352331-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 516756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 94 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465127.1. 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.-79-287A>G		intron	N/A	NP_001394021.1	P00480

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-313790A>G		intron	N/A	ENSP00000417050.1	B4E171
	OTC	ENST00000713758.1		c.-79-287A>G		intron	N/A	ENSP00000519059.1	P00480
	OTC	ENST00000909233.1		c.-79-287A>G		intron	N/A	ENSP00000579292.1

Frequencies

GnomAD3 genomes AF: 0.00345 AC: 386 AN: 111947 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.000715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00238

Gnomad ASJ AF: 0.00189

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000736

Gnomad FIN AF: 0.00313

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00577

Gnomad OTH AF: 0.00401

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

GnomAD4 genome AF: 0.00345 AC: 386 AN: 111999 Hom.: 1 Cov.: 24 AF XY: 0.00275 AC XY: 94 AN XY: 34157

African (AFR) AF: 0.000714 AC: 22 AN: 30824

American (AMR) AF: 0.00237 AC: 25 AN: 10536

Ashkenazi Jewish (ASJ) AF: 0.00189 AC: 5 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.000738 AC: 2 AN: 2710

European-Finnish (FIN) AF: 0.00313 AC: 19 AN: 6064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00577 AC: 307 AN: 53225

Other (OTH) AF: 0.00396 AC: 6 AN: 1516

Alfa AF: 0.00362 Hom.: 48

Bravo AF: 0.00329

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Ornithine carbamoyltransferase deficiency (3)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	OTC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		2.1
PromoterAI		0.0028	Neutral

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: rs191615506; hg19: chrX-38211584;