ClinVar Genomic variation as it relates to human health
NM_000048.4(ASL):c.392C>T (p.Thr131Met)
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
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NM_000048.4(ASL):c.392C>T (p.Thr131Met)
Variation ID: 203625 Accession: VCV000203625.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q11.21 7: 66083120 (GRCh38) [ NCBI UCSC ] 7: 65548107 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Dec 19, 2017 Feb 20, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000048.4:c.392C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000039.2:p.Thr131Met missense NM_001024943.2:c.392C>T NP_001020114.1:p.Thr131Met missense NM_001024944.2:c.392C>T NP_001020115.1:p.Thr131Met missense NM_001024946.2:c.392C>T NP_001020117.1:p.Thr131Met missense NC_000007.14:g.66083120C>T NC_000007.13:g.65548107C>T NG_009288.1:g.12332C>T - Protein change
- T131M
- Other names
- p.T131M:ACG>ATG
- Canonical SPDI
- NC_000007.14:66083119:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00300 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00042
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054
Trans-Omics for Precision Medicine (TOPMed) 0.00057
The Genome Aggregation Database (gnomAD), exomes 0.00235
Exome Aggregation Consortium (ExAC) 0.00248
1000 Genomes Project 0.00300
1000 Genomes Project 30x 0.00312
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 | ||
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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. |
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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. |
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Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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May 10, 2022 | RCV000185776.5 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000987893.13 |
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. |
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Likely benign
(Oct 25, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000238708.6
First in ClinVar: Jul 18, 2015 Last updated: Dec 19, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137382.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(-)
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criteria provided, single submitter
Method: research
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Argininosuccinate lyase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001435269.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The heterozygous p.Thr131Met variant in ASL has been identified in the compound heterozygous state state in a Turkish individual with argininosuccinate lyase deficiency (PMID: 12384776), … (more)
The heterozygous p.Thr131Met variant in ASL has been identified in the compound heterozygous state state in a Turkish individual with argininosuccinate lyase deficiency (PMID: 12384776), has been reported in at least 1 other individual not known to have disease (PMID: 25087612), and has been identified in >1% of South Asian chromosomes and 2 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive argininosuccinate lyase deficiency. (less)
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Benign
(Jul 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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Argininosuccinate lyase deficiency
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001748543.1
First in ClinVar: Jul 10, 2021 Last updated: Jul 10, 2021 |
Sex: mixed
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Benign
(May 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002547968.1
First in ClinVar: Jul 17, 2022 Last updated: Jul 17, 2022 |
Comment:
Variant summary: ASL c.392C>T (p.Thr131Met) results in a non-conservative amino acid change located in the Fumarate lyase, N-terminal domain (IPR022761) of the encoded protein sequence. … (more)
Variant summary: ASL c.392C>T (p.Thr131Met) results in a non-conservative amino acid change located in the Fumarate lyase, N-terminal domain (IPR022761) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0023 in 250460 control chromosomes, predominantly at a frequency of 0.015 within the South Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in ASL causing Argininosuccinic Aciduria phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as benign (n=3) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000756214.7
First in ClinVar: May 28, 2018 Last updated: Feb 20, 2024 |
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Benign
(Jun 11, 2020)
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no assertion criteria provided
Method: clinical testing
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Argininosuccinate lyase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001460127.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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 |
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Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results. | Tabor HK | American journal of human genetics | 2014 | PMID: 25087612 |
Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene. | Linnebank M | Human genetics | 2002 | PMID: 12384776 |
Text-mined citations for rs143793815 ...
HelpRecord last updated Mar 30, 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.