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NM_000048.4(ASL):c.690G>A (p.Met230Ile) AND Argininosuccinate lyase deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 3, 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:
RCV002042436.6

Allele description [Variation Report for NM_000048.4(ASL):c.690G>A (p.Met230Ile)]

NM_000048.4(ASL):c.690G>A (p.Met230Ile)

Gene:
ASL:argininosuccinate lyase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q11.21
Genomic location:
Preferred name:
NM_000048.4(ASL):c.690G>A (p.Met230Ile)
HGVS:
  • NC_000007.14:g.66087763G>A
  • NG_009288.1:g.16975G>A
  • NM_000048.4:c.690G>AMANE SELECT
  • NM_001024943.2:c.690G>A
  • NM_001024944.2:c.690G>A
  • NM_001024946.2:c.612G>A
  • NP_000039.2:p.Met230Ile
  • NP_001020114.1:p.Met230Ile
  • NP_001020115.1:p.Met230Ile
  • NP_001020117.1:p.Met204Ile
  • NC_000007.13:g.65552750G>A
Protein change:
M204I
Links:
dbSNP: rs2115733193
NCBI 1000 Genomes Browser:
rs2115733193
Molecular consequence:
  • NM_000048.4:c.690G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024943.2:c.690G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024944.2:c.690G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024946.2:c.612G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Argininosuccinate lyase deficiency
Synonyms:
Arginino succinase deficiency; Inborn error of urea synthesis, arginino succinic type; Urea cycle disorder, arginino succinase type; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008815; MedGen: C0268547; Orphanet: 23; OMIM: 207900; Human Phenotype Ontology: HP:0025630

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002291063Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Dec 3, 2021)
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. 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, SCV002291063.3

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 230 of the ASL protein (p.Met230Ile). 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. This variant disrupts the p.Met230 amino acid residue in ASL. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 ASL protein function. This variant has not been reported in the literature in individuals affected with ASL-related conditions. This variant is not present in population databases (gnomAD no frequency).

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

Last Updated: Sep 29, 2024