NM_001875.5(CPS1):c.2375del (p.Met792fs) AND Congenital hyperammonemia, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 23, 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:: RCV001043431.6

Allele description [Variation Report for NM_001875.5(CPS1):c.2375del (p.Met792fs)]

NM_001875.5(CPS1):c.2375del (p.Met792fs)

Gene:

CPS1:carbamoyl-phosphate synthase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q34

Genomic location:

Preferred name:

NM_001875.5(CPS1):c.2375del (p.Met792fs)

HGVS:

NC_000002.12:g.210608543del
NG_008285.1:g.135859del
NM_001122633.3:c.2375del
NM_001369256.1:c.2408del
NM_001369257.1:c.2375del
NM_001875.5:c.2375delMANE SELECT
NP_001116105.2:p.Met792fs
NP_001356185.1:p.Met803fs
NP_001356186.1:p.Met792fs
NP_001866.2:p.Met792fs
LRG_336t1:c.2375del
LRG_336:g.135859del
NC_000002.11:g.211473267del
NM_001875.4:c.2375del
NR_161225.1:n.3284del
NR_163592.1:n.1531del

Protein change:

M792fs

Links:

dbSNP: rs1699004800

NCBI 1000 Genomes Browser:

rs1699004800

Molecular consequence:

NM_001122633.3:c.2375del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369256.1:c.2408del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369257.1:c.2375del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001875.5:c.2375del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_161225.1:n.3284del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_163592.1:n.1531del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Congenital hyperammonemia, type I
Synonyms:: CPS I DEFICIENCY; Hyperammonemia due to carbamoyl phosphate synthetase 1 deficiency; CPS 1 deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009376; MedGen: C4082171; Orphanet: 147; OMIM: 237300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001207178	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 23, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21120950, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001207178

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 23, 2019)

germline

clinical testing

PubMed (2)
[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

Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations.

Häberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, Eeds A, Willis A, Yadav M, Summar S; Urea Cycle Disorders Consortium., Lichtarge O, Rubio V, Wong LJ, Summar M.

Hum Mutat. 2011 Jun;32(6):579-89. doi: 10.1002/humu.21406. Epub 2011 May 5.

PubMed [citation]

PMID:: 21120950
PMCID:: PMC4861085

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001207178.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CPS1 are known to be pathogenic (PMID: 21120950). This variant has not been reported in the literature in individuals with CPS1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met792Argfs*4) in the CPS1 gene. It is expected to result in an absent or disrupted protein product.

#	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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