NM_000531.6(OTC):c.621C>A (p.Ser207Arg) AND Ornithine carbamoyltransferase deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 6, 2021
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:: RCV003225028.2

Allele description [Variation Report for NM_000531.6(OTC):c.621C>A (p.Ser207Arg)]

NM_000531.6(OTC):c.621C>A (p.Ser207Arg)

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.621C>A (p.Ser207Arg)

HGVS:

NC_000023.11:g.38403698C>A
NG_008471.1:g.56216C>A
NM_000531.6:c.621C>AMANE SELECT
NP_000522.3:p.Ser207Arg
LRG_846t1:c.621C>A
LRG_846:g.56216C>A
LRG_846p1:p.Ser207Arg
NC_000023.10:g.38262951C>A
NM_000531.5:c.621C>A
P00480:p.Ser207Arg

Protein change:

S207R

Links:

UniProtKB: P00480#VAR_004907; dbSNP: rs72558415

NCBI 1000 Genomes Browser:

rs72558415

Molecular consequence:

NM_000531.6:c.621C>A - 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
SCV003921989	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 6, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9452024, 16786505, 17565723, 23278509, 26059767, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003921989

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 6, 2021)

germline

clinical testing

PubMed (6)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Ten novel mutations of the ornithine transcarbamylase (OTC) gene in OTC deficiency.

Shimadzu M, Matsumoto H, Matsuura T, Kobayashi K, Komaki S, Kiwaki K, Hoshide R, Endo F, Saheki T, Matsuda I.

Hum Mutat. 1998;Suppl 1:S5-7. No abstract available.

PubMed [citation]

PMID:: 9452024

Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene.

Yamaguchi S, Brailey LL, Morizono H, Bale AE, Tuchman M.

Hum Mutat. 2006 Jul;27(7):626-32.

PubMed [citation]

PMID:: 16786505

See all PubMed Citations (6)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV003921989.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with ornithine transcarbamylase deficiency. (I) 0109 - This gene is associated with X-linked recessive disease, however carrier females can be affected (PMID:26059767). (I) 0200 - Variant is predicted to result in a missense amino acid change from serine to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated aspartate/ornithine carbamoyl transferase domain (Pfam). (I) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. The variant p.(Ser207Asn) has been reported in multiple individuals with ornithine transcarbamylase deficiency (PMID: 17565723, 23278509, 16786505, ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. Two individuals with ornithine transcarbamylase deficiency have been reported with this variant (PMID:9452024, ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Aug 4, 2024

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