ClinVar Genomic variation as it relates to human health
NM_000045.4(ARG1):c.32T>C (p.Ile11Thr)
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_000045.4(ARG1):c.32T>C (p.Ile11Thr)
Variation ID: 2393 Accession: VCV000002393.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q23.2 6: 131573314 (GRCh38) [ NCBI UCSC ] 6: 131894454 (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 Jul 26, 2015 Jun 17, 2024 Mar 3, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000045.4:c.32T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000036.2:p.Ile11Thr missense NM_001244438.2:c.32T>C NP_001231367.1:p.Ile11Thr missense NM_001369020.1:c.32T>C NP_001355949.1:p.Ile11Thr missense NR_160934.1:n.89T>C non-coding transcript variant NC_000006.12:g.131573314T>C NC_000006.11:g.131894454T>C NG_007086.2:g.5090T>C NG_031860.2:g.59910A>G P05089:p.Ile11Thr - Protein change
- I11T
- Other names
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- Canonical SPDI
- NC_000006.12:131573313:T: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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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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ARG1 | - | - |
GRCh38 GRCh37 |
40 | 554 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 3, 2024 | RCV000002494.11 |
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
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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 pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Arginase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Lifecell International Pvt. Ltd
Accession: SCV003852659.1
First in ClinVar: Apr 09, 2023 Last updated: Apr 09, 2023 |
Comment:
A Homozygote Missense variant c.32T>C in Exon 1 of the ARG1 gene that results in the amino acid substitution p.Ile11Thr was identified. The observed variant … (more)
A Homozygote Missense variant c.32T>C in Exon 1 of the ARG1 gene that results in the amino acid substitution p.Ile11Thr was identified. The observed variant is novel in gnomAD exomes and genomes. The severity of the impact of this variant on the protein is medium, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic [Variation ID: 2393]. The observed variation has been previously reported in patients affected with hyperargininemia (Carvalho, Daniel Rocha et al., 2012). For these reasons, this variant has been classified as Likely Pathogenic. (less)
Ethnicity/Population group: Asian
Geographic origin: India
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Pathogenic
(Sep 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Arginase deficiency
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000631875.4
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ARG1 protein function. ClinVar contains an entry for this variant (Variation ID: 2393). This missense change has been observed in individual(s) with argininemia (PMID: 7649538, 21310339, 22959135, 26310552, 29443755). This variant is present in population databases (rs28941474, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 11 of the ARG1 protein (p.Ile11Thr). (less)
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Pathogenic
(Mar 03, 2024)
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criteria provided, single submitter
Method: clinical testing
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Arginase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV005054208.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Pathogenic
(Sep 01, 1995)
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no assertion criteria provided
Method: literature only
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ARGININEMIA
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022652.2
First in ClinVar: Apr 04, 2013 Last updated: Jul 26, 2015 |
Comment on evidence:
In 3 related Puerto Rican patients with arginase deficiency (207800), followed from 1 to 21 years of age by Snyderman et al. (1979), Uchino et … (more)
In 3 related Puerto Rican patients with arginase deficiency (207800), followed from 1 to 21 years of age by Snyderman et al. (1979), Uchino et al. (1995) identified a 32T-C change in exon 1 of the ARG1 gene, resulting in an ile11-to-thr (I11T) substitution. The patients were compound heterozygous for the I11T mutation and a G235R mutation (608313.0006). Functional expression studies in E. coli showed that the I11T mutant protein activity was 12% of normal arginase. The mutant arginase proteins previously analyzed, such as G235R and W122X (608313.0005), had less than 1% of the control activity in vitro. Response to dietary therapy was good. (less)
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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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Argininemia as a cause of severe chronic stunting and partial growth hormone deficiency (PGHD): A case report. | Cai X | Medicine | 2018 | PMID: 29443755 |
[Seven patients of argininemia with spastic tetraplegia as the first and major symptom and prenatal diagnosis of two fetuses with high risk]. | Wu T | Zhonghua er ke za zhi = Chinese journal of pediatrics | 2015 | PMID: 26310552 |
Analysis of novel ARG1 mutations causing hyperargininemia and correlation with arginase I activity in erythrocytes. | Carvalho DR | Gene | 2012 | PMID: 22959135 |
Argininemia presenting with progressive spastic diplegia. | Lee BH | Pediatric neurology | 2011 | PMID: 21310339 |
Molecular basis of phenotypic variation in patients with argininemia. | Uchino T | Human genetics | 1995 | PMID: 7649538 |
Argininemia treated from birth. | Snyderman SE | The Journal of pediatrics | 1979 | PMID: 480013 |
Text-mined citations for rs28941474 ...
HelpRecord last updated Sep 29, 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.