ClinVar Genomic variation as it relates to human health
NM_000016.6(ACADM):c.157C>T (p.Arg53Cys)
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_000016.6(ACADM):c.157C>T (p.Arg53Cys)
Variation ID: 92258 Accession: VCV000092258.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p31.1 1: 75732682 (GRCh38) [ NCBI UCSC ] 1: 76198367 (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 Jun 28, 2015 Feb 14, 2024 Jan 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000016.6:c.157C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000007.1:p.Arg53Cys missense NM_001127328.3:c.169C>T NP_001120800.1:p.Arg57Cys missense NM_001286042.2:c.49C>T NP_001272971.1:p.Arg17Cys missense NM_001286043.2:c.157C>T NP_001272972.1:p.Arg53Cys missense NM_001286044.2:c.-229C>T 5 prime UTR NC_000001.11:g.75732682C>T NC_000001.10:g.76198367C>T NG_007045.2:g.13325C>T LRG_838:g.13325C>T LRG_838t1:c.157C>T LRG_838p1:p.Arg53Cys P11310:p.Arg53Cys - Protein change
- R53C, R57C, R17C
- Other names
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- Canonical SPDI
- NC_000001.11:75732681: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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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
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
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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ACADM | - | - |
GRCh38 GRCh37 |
859 | 891 |
Conditions - Germline
Condition
Help
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 (2) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2016 | RCV000077882.17 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2024 | RCV000176961.30 |
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
(Feb 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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Medium-chain acyl-coenzyme A dehydrogenase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000268474.1
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893467.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Sep 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004216352.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000943514.6
First in ClinVar: Aug 13, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 53 of the ACADM protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 53 of the ACADM protein (p.Arg53Cys). This variant is present in population databases (rs398123072, gnomAD 0.02%). This missense change has been observed in individual(s) with MCAD deficiency (PMID: 8102510, 15832312, 16737882, 20434380, 22796001, 24623196). This variant is also known as R28C. ClinVar contains an entry for this variant (Variation ID: 92258). 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 ACADM protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ACADM function (PMID: 8102510, 26947917). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 15, 2016)
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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: SCV000329673.6
First in ClinVar: Dec 06, 2016 Last updated: Feb 15, 2018 |
Comment:
The R53C pathogenic variant in the ACADM gene has been reported previously in association with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (Derks et al., 2014). Expression … (more)
The R53C pathogenic variant in the ACADM gene has been reported previously in association with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (Derks et al., 2014). Expression studies found that R53C is associated with significantly reduced MCAD enzyme activity in comparison to wild type (Andresen et al., 1993; Bross et al., 1995). (less)
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Pathogenic
(Nov 16, 2012)
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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: SCV000228752.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 2
Sex: mixed
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Likely pathogenic
(Sep 23, 2016)
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no assertion criteria provided
Method: clinical testing
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Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000487011.2
First in ClinVar: Jun 28, 2015 Last updated: Dec 23, 2019 |
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Pathogenic
(May 03, 2017)
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no assertion criteria provided
Method: clinical testing
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Medium Chain Acyl-CoA Dehydrogenase Deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002092800.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Significance of ACADM mutations identified through newborn screening of MCAD deficiency in Japan. | Hara K | Molecular genetics and metabolism | 2016 | PMID: 26947917 |
Experimental evidence for protein oxidative damage and altered antioxidant defense in patients with medium-chain acyl-CoA dehydrogenase deficiency. | Derks TG | Journal of inherited metabolic disease | 2014 | PMID: 24623196 |
Clinical and molecular aspects of Japanese children with medium chain acyl-CoA dehydrogenase deficiency. | Purevsuren J | Molecular genetics and metabolism | 2012 | PMID: 22796001 |
Allelic diversity in MCAD deficiency: the biochemical classification of 54 variants identified during 5 years of ACADM sequencing. | Smith EH | Molecular genetics and metabolism | 2010 | PMID: 20434380 |
A novel tandem mass spectrometry method for rapid confirmation of medium- and very long-chain acyl-CoA dehydrogenase deficiency in newborns. | ter Veld F | PloS one | 2009 | PMID: 19649258 |
The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome. | Derks TG | The Journal of pediatrics | 2006 | PMID: 16737882 |
Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. | Maier EM | Human mutation | 2005 | PMID: 15832312 |
Comparison between medium-chain acyl-CoA dehydrogenase mutant proteins overexpressed in bacterial and mammalian cells. | Jensen TG | Human mutation | 1995 | PMID: 8535441 |
Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly, and stability of MCAD enzyme. | Bross P | The Journal of biological chemistry | 1995 | PMID: 7730333 |
A rare disease-associated mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene changes a conserved arginine, previously shown to be functionally essential in short-chain acyl-CoA dehydrogenase (SCAD). | Andresen BS | American journal of human genetics | 1993 | PMID: 8102510 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADM | - | - | - | - |
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Text-mined citations for rs398123072 ...
HelpRecord last updated Apr 20, 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.