NM_054012.4(ASS1):c.539G>A (p.Ser180Asn) AND Citrullinemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV001376618.4

Allele description [Variation Report for NM_054012.4(ASS1):c.539G>A (p.Ser180Asn)]

NM_054012.4(ASS1):c.539G>A (p.Ser180Asn)

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.539G>A (p.Ser180Asn)

Other names:

p.S180N:AGC>AAC; NM_000050.4(ASS1):c.539G>A(p.Ser180Asn); NM_054012.3(ASS1):c.539G>A(p.Ser180Asn)

HGVS:

NC_000009.12:g.130470877G>A
NG_011542.1:g.31171G>A
NM_000050.4:c.539G>A
NM_054012.4:c.539G>AMANE SELECT
NP_000041.2:p.Ser180Asn
NP_446464.1:p.Ser180Asn
NC_000009.11:g.133346264G>A
NM_054012.3:c.539G>A
P00966:p.Ser180Asn

Protein change:

S180N; SER180ASN

Links:

UniProtKB: P00966#VAR_000686; OMIM: 603470.0006; dbSNP: rs121908638

NCBI 1000 Genomes Browser:

rs121908638

Molecular consequence:

NM_000050.4:c.539G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_054012.4:c.539G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Citrullinemia
Synonyms:: Citrullinuria
Identifiers:: MONDO: MONDO:0015991; MedGen: C0175683; Human Phenotype Ontology: HP:0032397

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000630060	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 2358466, 18925679, 24765495, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000630060

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

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

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

The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia.

Dimmock DP, Trapane P, Feigenbaum A, Keegan CE, Cederbaum S, Gibson J, Gambello MJ, Vaux K, Ward P, Rice GM, Wolff JA, O'Brien WE, Fang P.

Am J Med Genet A. 2008 Nov 15;146A(22):2885-90. doi: 10.1002/ajmg.a.32527. Erratum in: Am J Med Genet A. 2010 Apr;152A(4):1061.

PubMed [citation]

PMID:: 18925679
PMCID:: PMC2597641

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000630060.7

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

Description

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 180 of the ASS1 protein (p.Ser180Asn). This variant is present in population databases (rs121908638, gnomAD 0.008%). This missense change has been observed in individual(s) with citrullinemia type I, including symptoms of hyperammonemia and markedly elevated plasma citrulline (PMID: 2358466, 18925679, 24765495; Invitae). ClinVar contains an entry for this variant (Variation ID: 6326). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ASS1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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: Apr 15, 2024

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