ClinVar Genomic variation as it relates to human health
NM_000048.4(ASL):c.1060C>T (p.Gln354Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000048.4(ASL):c.1060C>T (p.Gln354Ter)
Variation ID: 21253 Accession: VCV000021253.18
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7q11.21 7: 66089693 (GRCh38) [ NCBI UCSC ] 7: 65554680 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Apr 6, 2024 Mar 17, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000048.4:c.1060C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000039.2:p.Gln354Ter NM_001024943.2:c.1060C>T NP_001020114.1:p.Gln354Ter NM_001024944.2:c.1000C>T NP_001020115.1:p.Gln334Ter NM_001024946.2:c.982C>T NP_001020117.1:p.Gln328Ter NC_000007.14:g.66089693C>T NC_000007.13:g.65554680C>T NG_009288.1:g.18905C>T - Protein change
- Q354*, Q328*, Q334*
- Other names
- p.Q354*:CAG>TAG
- Canonical SPDI
- NC_000007.14:66089692:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
ASL | - | - |
GRCh38 GRCh37 |
840 | 875 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Mar 17, 2024 | RCV000020415.18 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 9, 2016 | RCV000078007.10 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 3, 2024 | RCV003914857.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(May 05, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694148.1
First in ClinVar: Feb 15, 2018 Last updated: Feb 15, 2018 |
Comment:
Variant summary: The c.1060C>T variant results in a premature termination codon, predicted to cause a truncated or absent ASL protein, which is a commonly known … (more)
Variant summary: The c.1060C>T variant results in a premature termination codon, predicted to cause a truncated or absent ASL protein, which is a commonly known mechanism for disease. One in-silico tool predicts damaging outcome for this variant. 4/5 splice prediction tools predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions are not confirmed by experimental studies.This variant is not found in 116646 control chromosomes. This variant has been reported in many affected individuals as a founder mutation in the Saudi population (Al-Sayed_JIMD_2005). In addition, multiple clinical laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic. (less)
|
|
Pathogenic
(Dec 30, 2017)
|
criteria provided, single submitter
Method: curation
|
Argininosuccinate lyase deficiency
Affected status: yes
Allele origin:
unknown
|
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University
Accession: SCV000891477.1
First in ClinVar: Feb 15, 2018 Last updated: Feb 15, 2018 |
Geographic origin: Middle East
|
|
Pathogenic
(Jan 03, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
ASL-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004730921.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The ASL c.1060C>T variant is predicted to result in premature protein termination (p.Gln354*). This variant was reported to be causative for argininosuccinic aciduria (Al-Sayed et … (more)
The ASL c.1060C>T variant is predicted to result in premature protein termination (p.Gln354*). This variant was reported to be causative for argininosuccinic aciduria (Al-Sayed et al. 2005. PubMed ID: 16435180; AlTassan et al. 2018. PubMed ID: 29326055). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in ASL are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
Pathogenic
(Sep 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000238699.7
First in ClinVar: Jul 18, 2015 Last updated: Dec 06, 2016 |
Comment:
p.Q354* CAG>TAG c.1060C>T nonsense variant in the ASL gene was identified in the homozygous state in 14 of 28 patients from Saudi Arabia who were … (more)
p.Q354* CAG>TAG c.1060C>T nonsense variant in the ASL gene was identified in the homozygous state in 14 of 28 patients from Saudi Arabia who were diagnosed with argininosuccinic aciduria (ASA) after being detected on MS/MS newborn screening (Al-Sayed et al., 2005). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. (less)
|
|
Pathogenic
(May 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000225991.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 5
Sex: mixed
|
|
Pathogenic
(Jul 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000485605.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 24, 2022 |
|
|
Pathogenic
(Oct 06, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002019529.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(May 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003440599.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln354*) in the ASL gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln354*) in the ASL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASL are known to be pathogenic (PMID: 2263616, 24166829). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with argininosuccinic aciduria (PMID: 16435180). ClinVar contains an entry for this variant (Variation ID: 21253). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 17, 2024)
|
criteria provided, single submitter
Method: research
|
Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004805173.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
|
|
Pathogenic
(Sep 26, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Argininosuccinate lyase deficiency
Affected status: yes
Allele origin:
germline
|
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001133190.1
First in ClinVar: Jan 06, 2020 Last updated: Jan 06, 2020 |
|
|
Pathogenic
(Nov 22, 2021)
|
no assertion criteria provided
Method: literature only
|
ARGININOSUCCINIC ACIDURIA
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV002026474.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
Comment on evidence:
In 26 of 35 Saudi Arabian patients with argininosuccinic aciduria (207900), AlTassan et al. (2018) identified homozygosity for a c.1060C-T transition in the ASL gene, … (more)
In 26 of 35 Saudi Arabian patients with argininosuccinic aciduria (207900), AlTassan et al. (2018) identified homozygosity for a c.1060C-T transition in the ASL gene, predicted to result in a gln354-to-ter (Q354X) substitution, suggesting that it is a founder mutation in this population. (less)
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Argininosuccinate lyase deficiency
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000040815.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Argininosuccinate Lyase Deficiency. | Adam MP | - | 2019 | PMID: 21290785 |
A retrospective biochemical, molecular, and neurocognitive review of Saudi patients with argininosuccinic aciduria. | AlTassan R | European journal of medical genetics | 2018 | PMID: 29326055 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
Mutations and polymorphisms in the human argininosuccinate lyase (ASL) gene. | Balmer C | Human mutation | 2014 | PMID: 24166829 |
Identification of a common novel mutation in Saudi patients with argininosuccinic aciduria. | Al-Sayed M | Journal of inherited metabolic disease | 2005 | PMID: 16435180 |
Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region. | Walker DC | Proceedings of the National Academy of Sciences of the United States of America | 1990 | PMID: 2263616 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ASL | - | - | - | - |
Text-mined citations for rs367543005 ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.