X-38352036-C-T

Position:

• chrX-38352036-C-T

Variant summary

Our verdict is Likely benign. Variant got -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

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 -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 id is 680700.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTC	NM_001407092.1	c.-79-582C>T		intron_variant			NP_001394021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1	c.172-314085C>T		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 78276 AN: 110957 Hom.: 19555 Cov.: 24 AF XY: 0.700 AC XY: 23321 AN XY: 33323

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

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.684

Alfa AF: 0.709 Hom.: 5695

Bravo AF: 0.705

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

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

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: rs5963412; hg19: chrX-38211289;