NM_000531.6(OTC):c.122A>G (p.Asp41Gly) AND Ornithine carbamoyltransferase deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 18, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001064676.6

Allele description [Variation Report for NM_000531.6(OTC):c.122A>G (p.Asp41Gly)]

NM_000531.6(OTC):c.122A>G (p.Asp41Gly)

Gene:

OTC:ornithine transcarbamylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_000531.6(OTC):c.122A>G (p.Asp41Gly)

HGVS:

NC_000023.11:g.38367335A>G
NG_008471.1:g.19853A>G
NM_000531.6:c.122A>GMANE SELECT
NP_000522.3:p.Asp41Gly
LRG_846t1:c.122A>G
LRG_846:g.19853A>G
LRG_846p1:p.Asp41Gly
NC_000023.10:g.38226588A>G
NM_000531.5:c.122A>G

Protein change:

D41G

Links:

dbSNP: rs74518351

NCBI 1000 Genomes Browser:

rs74518351

Molecular consequence:

NM_000531.6:c.122A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ornithine carbamoyltransferase deficiency (OTCD)
Synonyms:: ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO; Ornithine transcarbamylase deficiency; OTC deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010703; MedGen: C0268542; Orphanet: 664; OMIM: 311250

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001229589	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 18, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20458665, 19138872, 17334707, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001229589

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 18, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Management of ornithine transcarbamylase deficiency in pregnancy.

Mendez-Figueroa H, Lamance K, Sutton VR, Aagaard-Tillery K, Van den Veyver I.

Am J Perinatol. 2010 Nov;27(10):775-84. doi: 10.1055/s-0030-1254240. Epub 2010 May 10. Review.

PubMed [citation]

PMID:: 20458665

High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH.

Shchelochkov OA, Li FY, Geraghty MT, Gallagher RC, Van Hove JL, Lichter-Konecki U, Fernhoff PM, Copeland S, Reimschisel T, Cederbaum S, Lee B, Chinault AC, Wong LJ.

Mol Genet Metab. 2009 Mar;96(3):97-105. doi: 10.1016/j.ymgme.2008.11.167. Epub 2009 Jan 12.

PubMed [citation]

PMID:: 19138872

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001229589.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 20458665, 19138872, 17334707). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 97107). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 41 of the OTC protein (p.Asp41Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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