NM_000048.4(ASL):c.446+1G>A AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Feb 8, 2021
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:: RCV000078011.14

Allele description [Variation Report for NM_000048.4(ASL):c.446+1G>A]

NM_000048.4(ASL):c.446+1G>A

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.446+1G>A

HGVS:

NC_000007.14:g.66083175G>A
NG_009288.1:g.12387G>A
NM_000048.4:c.446+1G>AMANE SELECT
NM_001024943.2:c.446+1G>A
NM_001024944.2:c.446+1G>A
NM_001024946.2:c.446+1G>A
NC_000007.13:g.65548162G>A
NM_000048.3:c.446+1G>A
NM_001024943.1:c.446+1G>A

Nucleotide change:

IVS5DS, G-A, +1

Links:

OMIM: 608310.0003; dbSNP: rs142637046

NCBI 1000 Genomes Browser:

rs142637046

Molecular consequence:

NM_000048.4:c.446+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001024943.2:c.446+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001024944.2:c.446+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001024946.2:c.446+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000109849	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 22, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000238711	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 8, 2021)	germline	clinical testing	Citation Link,
SCV001920381	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
SCV001951975	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	Pathogenic	germline	clinical testing
SCV001975953	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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

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	2	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

Details of each submission

From Eurofins Ntd Llc (ga), SCV000109849.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From GeneDx, SCV000238711.7

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

Description

Canonical splice site variant predicted to result in a null allele and deletion of the upstream exon in a gene for which loss-of-function is a known mechanism of disease (Linnebank et al., 2002); Identified in a patient with late onset argininosuccinic aciduria who also harbored a second ASL variant (Baruteau et al., 2017); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25087612, 25525159, 24166829, 12384776, 28251416, 31589614)

#	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, SCV001920381.1

#	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, SCV001951975.1

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001975953.1

#	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

Last Updated: Sep 29, 2024

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