ClinVar Genomic variation as it relates to human health
NM_000017.4(ACADS):c.1054G>A (p.Ala352Thr)
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.
Likely pathogenic(1); Uncertain significance(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000017.4(ACADS):c.1054G>A (p.Ala352Thr)
Variation ID: 432218 Accession: VCV000432218.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q24.31 12: 120739164 (GRCh38) [ NCBI UCSC ] 12: 121176967 (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 Aug 20, 2017 Mar 16, 2024 Jan 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000017.4:c.1054G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000008.1:p.Ala352Thr missense NM_001302554.2:c.1042G>A NP_001289483.1:p.Ala348Thr missense NC_000012.12:g.120739164G>A NC_000012.11:g.121176967G>A NG_007991.1:g.18397G>A - Protein change
- A352T, A348T
- Other names
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- Canonical SPDI
- NC_000012.12:120739163:G:A
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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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0.00020 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Trans-Omics for Precision Medicine (TOPMed) 0.00007
- Links
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
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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
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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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ACADS | - | - |
GRCh38 GRCh37 |
442 | 461 |
Conditions - Germline
Condition
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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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Uncertain significance (1) |
criteria provided, single submitter
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Jun 9, 2017 | RCV000498121.1 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Jan 4, 2024 | RCV000673648.13 |
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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Uncertain significance
(Mar 27, 2018)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000798875.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Uncertain significance
(Jun 09, 2017)
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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: SCV000589916.3
First in ClinVar: Aug 20, 2017 Last updated: Aug 20, 2017 |
Comment:
The A352T variant was identified in a patient with short chain acyl-CoA dehydrogenase (SCAD) deficiency who was homozygous for both A352T and for the common … (more)
The A352T variant was identified in a patient with short chain acyl-CoA dehydrogenase (SCAD) deficiency who was homozygous for both A352T and for the common G209S variant which is a well studied variant known to confer susceptibility to develop SCAD deficiency (Rodolfo et al. 2016). The A352T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A352T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether the A352T variant is a pathogenic variant or a rare benign variant. (less)
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Uncertain significance
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of butyryl-CoA dehydrogenase
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002033271.1
First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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Likely pathogenic
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001543730.4
First in ClinVar: Mar 22, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 352 of the ACADS protein (p.Ala352Thr). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 352 of the ACADS protein (p.Ala352Thr). This variant is present in population databases (rs202078273, gnomAD 0.004%). This missense change has been observed in individuals with biochemical features of short chain acyl-CoA dehydrogenase (SCAD) deficiency (PMID: 27051597, 30612563). ClinVar contains an entry for this variant (Variation ID: 432218). 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 expected to disrupt ACADS protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Uncertain significance
(Aug 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002783195.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Deficiency of butyryl-CoA dehydrogenase
Affected status: yes
Allele origin:
germline
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Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital
Accession: SCV004800891.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
PM2_P+PM3_VS+PP3+PP4
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: Dong
Geographic origin: China
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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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A comprehensive multiplex PCR based exome-sequencing assay for rapid bloodspot confirmation of inborn errors of metabolism. | Wang W | BMC medical genetics | 2019 | PMID: 30612563 |
Clinical relevance of short-chain acyl-CoA dehydrogenase (SCAD) deficiency: Exploring the role of new variants including the first SCAD-disease-causing allele carrying a synonymous mutation. | Tonin R | BBA clinical | 2016 | PMID: 27051597 |
Mitochondrial fatty acid oxidation defects--remaining challenges. | Gregersen N | Journal of inherited metabolic disease | 2008 | PMID: 18836889 |
Text-mined citations for rs202078273 ...
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.