rs111060774

Positions:

• chrX-38408799-TGCTCTTTACATGTAAA-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000531.6(OTC):​c.717+8_717+23del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: OTC NM_000531.6 splice_donor_5th_base, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-38408799-TGCTCTTTACATGTAAA-T is Pathogenic according to our data. Variant chrX-38408799-TGCTCTTTACATGTAAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 97300.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTC	NM_000531.6	c.717+8_717+23del		splice_donor_5th_base_variant, intron_variant		ENST00000039007.5
OTC	NM_001407092.1	c.717+8_717+23del		splice_donor_5th_base_variant, intron_variant
OTC	XM_017029556.2	c.717+8_717+23del		splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTC	ENST00000039007.5	c.717+8_717+23del		splice_donor_5th_base_variant, intron_variant		1	NM_000531.6	P1
OTC	ENST00000643344.1	c.*467+8_*467+23del		splice_donor_5th_base_variant, intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

GenMed Metabolism Lab

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs111060774; hg19: chrX-38268052;