NM_000048.4(ASL):c.532G>A (p.Val178Met) AND not provided

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Feb 12, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000723377.16

Allele description [Variation Report for NM_000048.4(ASL):c.532G>A (p.Val178Met)]

NM_000048.4(ASL):c.532G>A (p.Val178Met)

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.532G>A (p.Val178Met)

HGVS:

NC_000007.14:g.66086751G>A
NG_009288.1:g.15963G>A
NM_000048.4:c.532G>AMANE SELECT
NM_001024943.2:c.532G>A
NM_001024944.2:c.532G>A
NM_001024946.2:c.524+89G>A
NP_000039.2:p.Val178Met
NP_001020114.1:p.Val178Met
NP_001020115.1:p.Val178Met
NC_000007.13:g.65551738G>A
NM_000048.3:c.532G>A
P04424:p.Val178Met

Protein change:

V178M; VAL178MET

Links:

UniProtKB: P04424#VAR_017572; OMIM: 608310.0005; dbSNP: rs28941473

NCBI 1000 Genomes Browser:

rs28941473

Molecular consequence:

NM_001024946.2:c.524+89G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000048.4:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001024943.2:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001024944.2:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000232467	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Mar 24, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12408190, 22231378 Citation Link,
SCV000238691	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 12, 2023)	germline	clinical testing	Citation Link,
SCV001739938	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001918675	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001954513	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV002525761	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 11, 2022)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 12384776, 12408190, 17326097, 19703900, 20236848, 21667091, 22231378, 24166829, 25778938, 31589614, 31943503, 31980526, 25741868
SCV005199587	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene.

Linnebank M, Tschiedel E, Häberle J, Linnebank A, Willenbring H, Kleijer WJ, Koch HG.

Hum Genet. 2002 Oct;111(4-5):350-9. Epub 2002 Aug 14.

PubMed [citation]

PMID:: 12384776

Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families.

Kleijer WJ, Garritsen VH, Linnebank M, Mooyer P, Huijmans JG, Mustonen A, Simola KO, Arslan-Kirchner M, Battini R, Briones P, Cardo E, Mandel H, Tschiedel E, Wanders RJ, Koch HG.

J Inherit Metab Dis. 2002 Sep;25(5):399-410.

PubMed [citation]

PMID:: 12408190

See all PubMed Citations (13)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000232467.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (2)

#	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		3	not provided	not provided	not provided

From GeneDx, SCV000238691.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies found this variant is associated with significantly reduced argininosuccinate lyase activity compared to wild-type (Engel et al., 2012; Doimo et al., 2012; Hu et al., 2015); This variant is associated with the following publications: (PMID: 28251416, 24166829, 17326097, 20236848, 34598035, 31589614, 22231378, 12384776, 19703900, 25778938, 31943503, 12408190, 31980526, 21667091)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001739938.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001918675.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001954513.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV002525761.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

PP4, PM2, PM3, PS3, PS4

#	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

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199587.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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