NM_001875.4(CPS1):c.586A>G (p.Asn196Asp) AND Congenital hyperammonemia, type I

Clinical significance:Uncertain significance (Last evaluated: May 21, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000707704.1

Allele description [Variation Report for NM_001875.4(CPS1):c.586A>G (p.Asn196Asp)]

NM_001875.4(CPS1):c.586A>G (p.Asn196Asp)

Gene:
CPS1:carbamoyl-phosphate synthase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q34
Genomic location:
Preferred name:
NM_001875.4(CPS1):c.586A>G (p.Asn196Asp)
HGVS:
  • NC_000002.12:g.210582674A>G
  • NG_008285.1:g.109990A>G
  • NM_001875.4:c.586A>G
  • NP_001866.2:p.Asn196Asp
  • LRG_336t1:c.586A>G
  • LRG_336:g.109990A>G
  • LRG_336p1:p.Asn196Asp
  • NC_000002.11:g.211447398A>G
Protein change:
N196D
Molecular consequence:
  • NM_001875.4:c.586A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital hyperammonemia, type I
Synonyms:
CPS I DEFICIENCY; Carbamoyl phosphate synthetase 1 deficiency
Identifiers:
MedGen: C4082171; Orphanet: 147; OMIM: 237300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000836813Invitaecriteria provided, single submitter
Uncertain significance
(May 21, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000836813.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces asparagine with aspartic acid at codon 196 of the CPS1 protein (p.Asn196Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs770935194, ExAC 0.002%). This variant has not been reported in the literature in individuals with CPS1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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