ClinVar Genomic variation as it relates to human health
NM_000666.3(ACY1):c.575dup (p.Ser192fs)
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_000666.3(ACY1):c.575dup (p.Ser192fs)
Variation ID: 800812 Accession: VCV000800812.45
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 3p21.2 3: 51986652-51986653 (GRCh38) [ NCBI UCSC ] 3: 52020668-52020669 (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 Jan 4, 2020 May 12, 2024 Nov 19, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000666.3:c.574_575insG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000666.3:c.575dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000657.1:p.Ser192fs frameshift NM_000666.2:c.575dupG NM_001198895.2:c.575dup NP_001185824.1:p.Ser192fs frameshift NM_001198896.2:c.359dup NP_001185825.1:p.Ser120fs frameshift NM_001198897.2:c.575dup NP_001185826.1:p.Ser192fs frameshift NM_001198898.2:c.470dup NP_001185827.1:p.Ser157fs frameshift NM_001316331.2:c.845dup NP_001303260.1:p.Ser282fs frameshift NC_000003.12:g.51986653dup NC_000003.11:g.52020669dup NG_012036.1:g.8107dup - Protein change
- S282fs, S120fs, S192fs, S157fs
- Other names
- -
- Canonical SPDI
- NC_000003.12:51986652:G:GG
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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.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Exome Aggregation Consortium (ExAC) 0.00009
The Genome Aggregation Database (gnomAD), exomes 0.00012
The Genome Aggregation Database (gnomAD) 0.00014
Trans-Omics for Precision Medicine (TOPMed) 0.00017
- Links
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
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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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ABHD14A-ACY1 | - | - | - | GRCh38 | - | 177 |
ACY1 | - | - |
GRCh38 GRCh37 |
1 | 162 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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 (4) |
criteria provided, multiple submitters, no conflicts
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Aug 26, 2021 | RCV000984988.5 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 19, 2023 | RCV001091093.28 |
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
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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
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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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Pathogenic
(Apr 07, 2019)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001714106.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PVS1, PS3, PM2, PM3, PP4
Number of individuals with the variant: 1
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Pathogenic
(Aug 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Aminoacylase 1 deficiency
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002784487.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Aminoacylase 1 deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Lifecell International Pvt. Ltd
Accession: SCV003923316.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
A Homozygote Frameshift variant c.574_575insG in Exon 8 of the ACY1 gene was identified. The variant is predicted to cause a frameshift and consequent premature … (more)
A Homozygote Frameshift variant c.574_575insG in Exon 8 of the ACY1 gene was identified. The variant is predicted to cause a frameshift and consequent premature termination of the protein (p.Ser192fs*64). The observed variant has a minor allele frequency of 0.00012% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, 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. The variant was found in ClinVar (Variant ID :800812) with a classification of Pathogenic and a review status of (2 star) criteria provided, multiple submitters, no conflicts. The variant has been previously reported in patients with ACY1D (Alessandrì MG et al.,2014). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. (less)
Ethnicity/Population group: Asian
Geographic origin: India
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Likely pathogenic
(Mar 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV004014262.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34426522, 31980526, 24367280, 29653693, 24997716, 35112591) (less)
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Pathogenic
(Nov 19, 2023)
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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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Invitae
Accession: SCV003295523.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser192Argfs*64) in the ACY1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser192Argfs*64) in the ACY1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACY1 are known to be pathogenic (PMID: 16465618, 21414403, 24997716). This variant is present in population databases (rs770702363, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with aminoacylase 1 deficiency (PMID: 24997716, 31980526). ClinVar contains an entry for this variant (Variation ID: 800812). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246944.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 3
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Pathogenic
(Aug 25, 2019)
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no assertion criteria provided
Method: clinical testing
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Aminoacylase 1 deficiency
Affected status: yes
Allele origin:
germline
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Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001132914.1
First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020 |
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Pathogenic
(Apr 01, 2023)
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no assertion criteria provided
Method: clinical testing
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Aminoacylase 1 deficiency
Affected status: yes
Allele origin:
germline
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Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)
Accession: SCV003927903.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
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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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Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. | Hou YC | Proceedings of the National Academy of Sciences of the United States of America | 2020 | PMID: 31980526 |
Four years follow up of ACY1 deficient patient and pedigree study. | Alessandrì MG | Brain & development | 2018 | PMID: 29653693 |
Isolated mild intellectual disability expands the aminoacylase 1 phenotype spectrum. | Alessandrì MG | JIMD reports | 2014 | PMID: 24997716 |
The molecular basis of aminoacylase 1 deficiency. | Sommer A | Biochimica et biophysica acta | 2011 | PMID: 21414403 |
Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. | Sass JO | American journal of human genetics | 2006 | PMID: 16465618 |
Text-mined citations for rs770702363 ...
HelpRecord last updated May 12, 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.