X-38412940-T-C

Position:

• chrX-38412940-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000531.6(OTC):​c.1005+941T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 110,358 control chromosomes in the GnomAD database, including 12,162 homozygotes. There are 16,506 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (12162 hom., 16506 hem., cov: 22)
• Consequence: OTC NM_000531.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.524

Genes affected

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant X-38412940-T-C is Benign according to our data. Variant chrX-38412940-T-C is described in ClinVar as [Benign]. Clinvar id is 680703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTC	NM_000531.6	c.1005+941T>C		intron_variant		ENST00000039007.5	NP_000522.3
OTC	NM_001407092.1	c.1005+941T>C		intron_variant			NP_001394021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTC	ENST00000039007.5	c.1005+941T>C		intron_variant		1	NM_000531.6	ENSP00000039007.4
ENSG00000250349	ENST00000465127.1	c.172-253181T>C		intron_variant		5		ENSP00000417050.1
OTC	ENST00000643344.1	n.*755+941T>C		intron_variant				ENSP00000496606.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 56556 AN: 110302 Hom.: 12151 Cov.: 22 AF XY: 0.505 AC XY: 16448 AN XY: 32552

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.513 AC: 56631 AN: 110358 Hom.: 12162 Cov.: 22 AF XY: 0.506 AC XY: 16506 AN XY: 32618

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.455

Alfa AF: 0.480 Hom.: 5759

Bravo AF: 0.539

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	-0.95
CADD	Benign	1.0
DANN	Benign	0.56

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: rs5963419; hg19: chrX-38272193;