NM_054012.4(ASS1):c.40G>A (p.Gly14Ser) AND Citrullinemia

Clinical significance:Likely pathogenic (Last evaluated: Feb 10, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001376548.1

Allele description [Variation Report for NM_054012.4(ASS1):c.40G>A (p.Gly14Ser)]

NM_054012.4(ASS1):c.40G>A (p.Gly14Ser)

Gene:
ASS1:argininosuccinate synthase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_054012.4(ASS1):c.40G>A (p.Gly14Ser)
HGVS:
  • NC_000009.12:g.130452268G>A
  • NG_011542.1:g.12562G>A
  • NM_000050.4:c.40G>A
  • NM_054012.4:c.40G>AMANE SELECT
  • NP_000041.2:p.Gly14Ser
  • NP_446464.1:p.Gly14Ser
  • NC_000009.11:g.133327655G>A
  • P00966:p.Gly14Ser
Protein change:
G14S; GLY14SER
Links:
UniProtKB: P00966#VAR_000681; OMIM: 603470.0004; dbSNP: rs121908636
NCBI 1000 Genomes Browser:
rs121908636
Molecular consequence:
  • NM_000050.4:c.40G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_054012.4:c.40G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Citrullinemia (CTNL1)
Identifiers:
MONDO: MONDO:0015991; MedGen: C0175683

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001208612Invitaecriteria provided, single submitter
Likely pathogenic
(Feb 10, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia.

Kobayashi K, Jackson MJ, Tick DB, O'Brien WE, Beaudet AL.

J Biol Chem. 1990 Jul 5;265(19):11361-7.

PubMed [citation]
PMID:
2358466

Kinetic mutations in argininosuccinate synthetase deficiency: characterisation and in vitro correction by substrate supplementation.

Diez-Fernandez C, Wellauer O, Gemperle C, Rüfenacht V, Fingerhut R, Häberle J.

J Med Genet. 2016 Oct;53(10):710-9. doi: 10.1136/jmedgenet-2016-103937. Epub 2016 Jun 10.

PubMed [citation]
PMID:
27287393
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001208612.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces glycine with serine at codon 14 of the ASS1 protein (p.Gly14Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs121908636, ExAC 0.03%). This variant has been observed in several individuals affected with citrullinemia type I (PMID: 2358466, 27287393, 14680976, 28111830, 23246278). ClinVar contains an entry for this variant (Variation ID: 6324). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Oct 7, 2021

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