Variant X-38401276-G-GTAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4_SupportingPP3PP5

The NM_000531.6(OTC):c.390_392dup(p.Leu131_Ser131insLeu) variant causes a inframe insertion, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. V130V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)

Consequence

OTC
NM_000531.6 inframe_insertion, splice_region

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.63

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a hotspot region, there are 8 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 8 uncertain in NM_000531.6

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000531.6. Strenght limited to Supporting due to length of the change: 1aa.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

PP5

Variant X-38401276-G-GTAT is Pathogenic according to our data. Variant chrX-38401276-G-GTAT is described in ClinVar as [Pathogenic]. Clinvar id is 97185.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OTC	NM_000531.6 linkuse as main transcript	c.390_392dup	p.Leu131_Ser131insLeu	inframe_insertion, splice_region_variant	5/10	ENST00000039007.5
OTC	NM_001407092.1 linkuse as main transcript	c.390_392dup	p.Leu131_Ser131insLeu	inframe_insertion, splice_region_variant	7/12
OTC	XM_017029556.2 linkuse as main transcript	c.390_392dup	p.Leu131_Ser131insLeu	inframe_insertion, splice_region_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OTC	ENST00000039007.5 linkuse as main transcript	c.390_392dup	p.Leu131_Ser131insLeu	inframe_insertion, splice_region_variant	5/10	1	NM_000531.6	P1
OTC	ENST00000488812.1 linkuse as main transcript	n.427_429dup		splice_region_variant, non_coding_transcript_exon_variant	5/6	5
OTC	ENST00000643344.1 linkuse as main transcript	c.140_142dup		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	6/11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

GenMed Metabolism Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over