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: 27054707, 29402417)
ClinVar Genomic variation as it relates to human health
NM_000016.6(ACADM):c.984del (p.Met328fs)
Germline
Classification
Help
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.
(7)
Help
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.
Pathogenic/Likely pathogenic
7
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000016.6(ACADM):c.984del (p.Met328fs)
Variation ID: 226096 Accession: VCV000226096.21
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 1p31.1 1: 75761160 (GRCh38) [ NCBI UCSC ] 1: 76226845 (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 May 21, 2016 Jun 17, 2024 Feb 16, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000016.6:c.984del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000007.1:p.Met328fs frameshift NM_000016.6:c.984delG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000016.5:c.984delG NM_001127328.3:c.996del NP_001120800.1:p.Met332fs frameshift NM_001286042.2:c.876del NP_001272971.1:p.Met292fs frameshift NM_001286043.2:c.1083del NP_001272972.1:p.Met361fs frameshift NM_001286044.2:c.417del NP_001272973.1:p.Met139fs frameshift NC_000001.11:g.75761160del NC_000001.10:g.76226845del NG_007045.2:g.41803del LRG_838:g.41803del LRG_838t1:c.984del LRG_838p1:p.Met328fs - Protein change
- M328fs, M332fs, M292fs, M139fs, M361fs
- Other names
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- Canonical SPDI
- NC_000001.11:75761159:G:
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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
Help
The frequency of the allele represented by this VCV record.
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Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
- 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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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
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. |
|||
| ACADM | - | - |
GRCh38 GRCh37 |
892 | 924 | |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Feb 16, 2024 | RCV000211482.20 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 3, 2020 | RCV001567614.3 |
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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|---|---|---|---|---|---|
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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
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000268490.1
First in ClinVar: May 21, 2016 Last updated: May 21, 2016 |
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Likely pathogenic
(Nov 07, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000795383.1
First in ClinVar: May 21, 2016 Last updated: May 21, 2016 |
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Pathogenic
(Dec 03, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001791333.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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 disease; This … (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: 27054707, 29402417) (less)
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Medium-chain acyl-coenzyme A dehydrogenase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004100487.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
Comment:
The frameshift deletion p.M328Ifs*5 in ACADM (NM_000016.6) has been reported to Clin Var as Pathogenic/Likely Pathogenic. It has not been reported in literature in affected … (more)
The frameshift deletion p.M328Ifs*5 in ACADM (NM_000016.6) has been reported to Clin Var as Pathogenic/Likely Pathogenic. It has not been reported in literature in affected individuals. The p.M328Ifs*5 variant is observed in 6/30,612 (0.0196%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Likely Pathogenic. (less)
Clinical Features:
Global developmental delay (present) , Cerebellar ataxia (present) , Aphasia (present) , Delayed ability to crawl (present) , Dysphagia (present) , Reduced eye contact (present) … (more)
Global developmental delay (present) , Cerebellar ataxia (present) , Aphasia (present) , Delayed ability to crawl (present) , Dysphagia (present) , Reduced eye contact (present) , Jaundice (present) , Abnormal metabolism (present) , Reduced tissue carnitine O-palmitoyltransferase 2 activity (present) , Bilateral choanal atresia (present) (less)
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Pathogenic
(Sep 12, 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
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000941321.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 226096). This variant has not been … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 226096). This variant has not been reported in the literature in individuals affected with ACADM-related conditions. This variant is present in population databases (rs747610156, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Met328Ilefs*5) in the ACADM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380). (less)
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Likely pathogenic
(Feb 16, 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:
unknown
|
Baylor Genetics
Accession: SCV004210759.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Sep 16, 2020)
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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:
germline
|
Natera, Inc.
Accession: SCV001461472.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
Comment:
Comment:
The frameshift deletion p.M328Ifs*5 in ACADM (NM_000016.6) has been reported to Clin Var as Pathogenic/Likely Pathogenic. It has not been reported in literature in affected individuals. The p.M328Ifs*5 variant is observed in 6/30,612 (0.0196%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Likely Pathogenic.
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 226096). This variant has not been reported in the literature in individuals affected with ACADM-related conditions. This variant is present in population databases (rs747610156, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Met328Ilefs*5) in the ACADM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380).
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. |
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 disease; This variant is associated with the following publications: (PMID: 27054707, 29402417)
Comment:
The frameshift deletion p.M328Ifs*5 in ACADM (NM_000016.6) has been reported to Clin Var as Pathogenic/Likely Pathogenic. It has not been reported in literature in affected individuals. The p.M328Ifs*5 variant is observed in 6/30,612 (0.0196%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Likely Pathogenic.
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 226096). This variant has not been reported in the literature in individuals affected with ACADM-related conditions. This variant is present in population databases (rs747610156, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Met328Ilefs*5) in the ACADM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Medium-chain acyl-CoA dehydrogenase deficiency in gene-targeted mice. | Tolwani RJ | PLoS genetics | 2005 | PMID: 16121256 |
Text-mined citations for rs747610156 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record 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.