rs5963030

Variant names:

• chrX-38352332-G-A
• rs5963030
• ENST00000465127.1:c.172-313789G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001407092.1(OTC):​c.-79-286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 111,471 control chromosomes in the GnomAD database, including 807 homozygotes. There are 4,317 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (807 hom., 4317 hem., cov: 24)
• Consequence: OTC NM_001407092.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.552
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-38352332-G-A is Benign according to our data. Variant chrX-38352332-G-A is described in ClinVar as Benign. ClinVar VariationId is 380178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407092.1. 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.-79-286G>A		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.172-313789G>A		intron	N/A	ENSP00000417050.1	B4E171
	OTC	ENST00000713758.1		c.-79-286G>A		intron	N/A	ENSP00000519059.1	P00480
	OTC	ENST00000909233.1		c.-79-286G>A		intron	N/A	ENSP00000579292.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 14878 AN: 111418 Hom.: 806 Cov.: 24

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.134 AC: 14890 AN: 111471 Hom.: 807 Cov.: 24 AF XY: 0.128 AC XY: 4317 AN XY: 33687

African (AFR) AF: 0.0878 AC: 2696 AN: 30705

American (AMR) AF: 0.101 AC: 1062 AN: 10485

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 449 AN: 2641

East Asian (EAS) AF: 0.0583 AC: 207 AN: 3553

South Asian (SAS) AF: 0.166 AC: 443 AN: 2672

European-Finnish (FIN) AF: 0.141 AC: 840 AN: 5944

Middle Eastern (MID) AF: 0.162 AC: 35 AN: 216

European-Non Finnish (NFE) AF: 0.168 AC: 8903 AN: 53072

Other (OTH) AF: 0.112 AC: 168 AN: 1499

Alfa AF: 0.153 Hom.: 1306

Bravo AF: 0.125

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	Ornithine carbamoyltransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.70
PhyloP100		0.55
PromoterAI		-0.00040	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: rs5963030; hg19: chrX-38211585;