ClinVar Genomic variation as it relates to human health
NM_000016.6(ACADM):c.388-5G>A
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_000016.6(ACADM):c.388-5G>A
Variation ID: 281016 Accession: VCV000281016.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p31.1 1: 75734786 (GRCh38) [ NCBI UCSC ] 1: 76200471 (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 Feb 14, 2024 Aug 27, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000016.6:c.388-5G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001127328.3:c.400-5G>A intron variant NM_001286042.2:c.280-5G>A intron variant NM_001286043.2:c.487-5G>A intron variant NM_001286044.2:c.-100+1864G>A intron variant NC_000001.11:g.75734786G>A NC_000001.10:g.76200471G>A NG_007045.2:g.15429G>A LRG_838:g.15429G>A LRG_838t1:c.388-5G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000001.11:75734785: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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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00004
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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ACADM | - | - |
GRCh38 GRCh37 |
859 | 891 |
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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jan 22, 2020 | RCV000498502.6 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Aug 27, 2023 | RCV000665148.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 3, 2022 | RCV002298560.1 |
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
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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
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
(Oct 01, 2015)
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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: SCV000331059.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Jan 19, 2017)
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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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Counsyl
Accession: SCV000789217.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Uncertain significance
(Jan 22, 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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GeneDx
Accession: SCV000589301.3
First in ClinVar: Aug 20, 2017 Last updated: Dec 15, 2018 |
Comment:
In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek … (more)
In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21083904) (less)
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Uncertain significance
(Sep 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002598541.1
First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022 |
Comment:
Variant summary: ACADM c.388-5G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more)
Variant summary: ACADM c.388-5G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a new 3' acceptor site three base pairs upstream from the canonical splice site. Two predict the variant abolishes the canonical 3' acceptor site and one predicts the variant weakens the canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 250272 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.388-5G>A has been reported in the literature as a biallelic genotype in at least one individual affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency (Kennedy_2010). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: three classify the variant as uncertain significance and one as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Likely pathogenic
(Aug 27, 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:
germline
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Invitae
Accession: SCV001576249.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 281016). This sequence change falls in intron 5 of the ACADM gene. It does not directly … (more)
ClinVar contains an entry for this variant (Variation ID: 281016). This sequence change falls in intron 5 of the ACADM gene. It does not directly change the encoded amino acid sequence of the ACADM protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with MCAD deficiency (PMID: 21083904; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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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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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The role of exome sequencing in newborn screening for inborn errors of metabolism. | Adhikari AN | Nature medicine | 2020 | PMID: 32778825 |
The first three years of screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) by newborn screening ontario. | Kennedy S | BMC pediatrics | 2010 | PMID: 21083904 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADM | - | - | - | - |
Text-mined citations for rs759254037 ...
HelpRecord last updated Feb 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.