ClinVar Genomic variation as it relates to human health
NM_054012.4(ASS1):c.1194-1G>C
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_054012.4(ASS1):c.1194-1G>C
Variation ID: 166704 Accession: VCV000166704.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q34.11 9: 130500975 (GRCh38) [ NCBI UCSC ] 9: 133376362 (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 Mar 29, 2015 Feb 14, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_054012.4:c.1194-1G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_000050.4:c.1194-1G>C splice acceptor NC_000009.12:g.130500975G>C NC_000009.11:g.133376362G>C NG_011542.1:g.61269G>C - Protein change
- Other names
- IVS15, G-C, -1
- Canonical SPDI
- NC_000009.12:130500974:G:C
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00005
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
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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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ASS1 | - | - |
GRCh38 GRCh37 |
793 | 846 |
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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Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Nov 16, 2021 | RCV000152808.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 1, 2014 | RCV000723939.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV001376639.4 |
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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Pathogenic
(Jan 19, 2017)
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criteria provided, single submitter
Method: clinical testing
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Citrullinemia
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694162.1
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
Comment:
Variant summary: The ASS1 c.1194-1G>C variant involves the alteration of a conserved intronic nucleotide located at a position known to affect splicing, which 5/5 splice … (more)
Variant summary: The ASS1 c.1194-1G>C variant involves the alteration of a conserved intronic nucleotide located at a position known to affect splicing, which 5/5 splice prediction tools predict a significant impact on normal splicing and ESE finder predicts alterations to ESE binding. A functional study, Su_1990, indicates the variant to affect splicing and cause an elongation of the protein. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/121348 (1/60674), which does not exceed the estimated maximal expected allele frequency for a pathogenic ASS1 variant of 1/244. Multiple publications have cited the variant in affected individuals as homozygotes and compound heterozygotes, along with multiple clinical diagnostic laboratories classifying the variant as "likely pathogenic/pathogenic." Therefore, the variant of interest has been classified as "Pathogenic." (less)
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Pathogenic
(Apr 01, 2014)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000202202.7
First in ClinVar: Jan 31, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Citrullinemia type I
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163605.1
First in ClinVar: Feb 28, 2020 Last updated: Feb 28, 2020 |
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Pathogenic
(Nov 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Citrullinemia type I
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003811045.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Citrullinemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000818059.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 15 of the ASS1 gene. RNA analysis indicates that disruption of this splice site induces … (more)
This sequence change affects an acceptor splice site in intron 15 of the ASS1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs727503814, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with citrullinemia (PMID: 2246255, 2358466, 15266621, 15334737, 24889030). ClinVar contains an entry for this variant (Variation ID: 166704). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in 7 bp deletion of exon 16 and introduces a new termination codon (PMID: 17576681). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 15, 2004)
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no assertion criteria provided
Method: literature only
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CITRULLINEMIA, CLASSIC
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026901.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 20, 2016 |
Comment on evidence:
In a patient with neonatal citrullinemia (215700), Kobayashi et al. (1990) found a G-to-C transversion in the last nucleotide of intron 15 of the ASS … (more)
In a patient with neonatal citrullinemia (215700), Kobayashi et al. (1990) found a G-to-C transversion in the last nucleotide of intron 15 of the ASS gene. The mutation resulted in a 7-base deletion in exon 16 of ASS mRNA. Potter et al. (2004) found this mutation in compound heterozygosity with a novel missense mutation (603470.0019) in an adult female patient, diagnosed through newborn screening, who underwent 2 successful pregnancies. Gucer et al. (2004) identified this homozygous splice site mutation in a girl with severe neonatal citrullinemia who died at age 17 months of early liver cirrhosis and hepatic encephalopathy. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Citrullinemia type I
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001453095.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(Aug 16, 2017)
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no assertion criteria provided
Method: clinical testing
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Citrullinemia type I
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000221057.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 23, 2019 |
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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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Improved standards for prenatal diagnosis of citrullinemia. | Miller MJ | Molecular genetics and metabolism | 2014 | PMID: 24889030 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Early cirrhosis in a patient with type I citrullinaemia (CTLN1). | Güçer S | Journal of inherited metabolic disease | 2004 | PMID: 15334737 |
Pregnancy in a healthy woman with untreated citrullinemia. | Potter MA | American journal of medical genetics. Part A | 2004 | PMID: 15266621 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. | Kobayashi K | The Journal of biological chemistry | 1990 | PMID: 2358466 |
Analysis of a splice acceptor site mutation which produces multiple splicing abnormalities in the human argininosuccinate synthetase locus. | Su TS | The Journal of biological chemistry | 1990 | PMID: 2246255 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ASS1 | - | - | - | - |
Text-mined citations for rs727503814 ...
HelpRecord last updated Mar 17, 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.