ENST00000465127.1:c.172-314085C>T

Variant names:

• chrX-38352036-C-T
• rs5963412
• ENST00000465127.1:c.172-314085C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000465127.1(ENSG00000250349):​c.172-314085C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (19549 hom., 23366 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant X-38352036-C-T is Benign according to our data. Variant chrX-38352036-C-T is described in ClinVar as Benign. ClinVar VariationId is 680700.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-79-582C>T		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.172-314085C>T		intron	N/A	ENSP00000417050.1	B4E171
	OTC	ENST00000713758.1		c.-79-582C>T		intron	N/A	ENSP00000519059.1	P00480
	OTC	ENST00000909233.1		c.-79-582C>T		intron	N/A	ENSP00000579292.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 78276 AN: 110957 Hom.: 19555 Cov.: 24

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.717

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: 0.705 AC: 78312 AN: 111013 Hom.: 19549 Cov.: 24 AF XY: 0.700 AC XY: 23366 AN XY: 33389

African (AFR) AF: 0.687 AC: 20981 AN: 30533

American (AMR) AF: 0.694 AC: 7305 AN: 10521

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2060 AN: 2639

East Asian (EAS) AF: 0.724 AC: 2530 AN: 3493

South Asian (SAS) AF: 0.762 AC: 2034 AN: 2670

European-Finnish (FIN) AF: 0.634 AC: 3733 AN: 5884

Middle Eastern (MID) AF: 0.799 AC: 171 AN: 214

European-Non Finnish (NFE) AF: 0.717 AC: 37936 AN: 52880

Other (OTH) AF: 0.684 AC: 1031 AN: 1507

Alfa AF: 0.709 Hom.: 5695

Bravo AF: 0.705

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.33
PhyloP100		-3.2

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: rs5963412; hg19: chrX-38211289;