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

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

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 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 rank	MANE	Protein	UniProt
OTC	NM_000531.6	c.1005+941T>C		intron_variant	Intron 9 of 9	ENST00000039007.5	NP_000522.3
OTC	NM_001407092.1	c.1005+941T>C		intron_variant	Intron 11 of 11		NP_001394021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTC	ENST00000039007.5	c.1005+941T>C		intron_variant	Intron 9 of 9	1	NM_000531.6	ENSP00000039007.4
ENSG00000250349	ENST00000465127.1	c.172-253181T>C		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
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

Publications

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Other links and lift over

dbSNP: rs5963419; hg19: chrX-38272193;