chrX-38412940-T-C

Variant names:

• chrX-38412940-T-C
• rs5963419
• NM_000531.6:c.1005+941T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

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)

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000531.6. 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_000531.6	MANE Select	c.1005+941T>C		intron	N/A	NP_000522.3
	OTC	NM_001407092.1		c.1005+941T>C		intron	N/A	NP_001394021.1	P00480

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTC	ENST00000039007.5	TSL:1 MANE Select	c.1005+941T>C		intron	N/A	ENSP00000039007.4	P00480
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-253181T>C		intron	N/A	ENSP00000417050.1	B4E171
	OTC	ENST00000713758.1		c.1005+941T>C		intron	N/A	ENSP00000519059.1	P00480

Frequencies

GnomAD3 genomes AF: 0.513 AC: 56556 AN: 110302 Hom.: 12151 Cov.: 22

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

African (AFR) AF: 0.823 AC: 24938 AN: 30293

American (AMR) AF: 0.502 AC: 5200 AN: 10359

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1075 AN: 2618

East Asian (EAS) AF: 0.639 AC: 2210 AN: 3456

South Asian (SAS) AF: 0.613 AC: 1588 AN: 2590

European-Finnish (FIN) AF: 0.375 AC: 2196 AN: 5863

Middle Eastern (MID) AF: 0.343 AC: 72 AN: 210

European-Non Finnish (NFE) AF: 0.352 AC: 18568 AN: 52778

Other (OTH) AF: 0.455 AC: 687 AN: 1510

Alfa AF: 0.501 Hom.: 10907

Bravo AF: 0.539

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	-0.95
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs5963419; hg19: chrX-38272193;