ClinVar Genomic variation as it relates to human health
NM_000016.6(ACADM):c.449_452del (p.Thr150fs)
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.449_452del (p.Thr150fs)
Variation ID: 189036 Accession: VCV000189036.54
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 1p31.1 1: 75734849-75734852 (GRCh38) [ NCBI UCSC ] 1: 76200534-76200537 (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 Mar 29, 2015 Apr 15, 2024 Jan 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000016.6:c.449_452del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000007.1:p.Thr150fs frameshift NM_000016.6:c.449_452delCTGA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_000016.4:c.446_449delTGAC NM_000016.5:c.449_452delCTGA frameshift NM_001127328.3:c.461_464del NP_001120800.1:p.Thr154fs frameshift NM_001286042.2:c.341_344del NP_001272971.1:p.Thr114fs frameshift NM_001286043.2:c.548_551del NP_001272972.1:p.Thr183fs frameshift NM_001286044.2:c.-100+1930_-100+1933del intron variant NC_000001.11:g.75734852_75734855del NC_000001.10:g.76200537_76200540del NG_007045.2:g.15495_15498del LRG_838:g.15495_15498del LRG_838t1:c.449_452del LRG_838p1:p.Thr150fs - Protein change
- T150fs, T154fs, T183fs, T114fs
- Other names
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- Canonical SPDI
- NC_000001.11:75734848:TGACTGA:TGA
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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.
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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
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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 |
863 | 895 |
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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Pathogenic (10) |
criteria provided, multiple submitters, no conflicts
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Jan 26, 2024 | RCV000169427.29 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 22, 2022 | RCV000723370.8 |
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
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: SCV000268448.1
First in ClinVar: May 20, 2016 Last updated: May 20, 2016 |
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Pathogenic
(Mar 02, 2017)
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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: SCV000700258.2
First in ClinVar: Dec 15, 2018 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Sep 09, 2019)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361312.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: ACADM c.449_452delCTGA (p.Thr150ArgfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: ACADM c.449_452delCTGA (p.Thr150ArgfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2e-05 in 251336 control chromosomes (gnomAD). c.449_452delCTGA has been reported in the literature in compound heterozygous and homozygous individuals affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency (Ensenauer_2005, Purevsuren_2009). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 28, 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: SCV004212147.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220052.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant alters the translational reading frame of the ACADM mRNA and causes the premature termination of ACADM protein synthesis. The frequency of this … (more)
This frameshift variant alters the translational reading frame of the ACADM mRNA and causes the premature termination of ACADM protein synthesis. The frequency of this variant in the general population, 0.00027 (5/18392 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (PMID: 15915086 (2005), 19064330 (2009), 21239873 (2011), 22796001 (2012), 25503862 (2015), 27856190 (2016), and 33841490 (2021)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 26, 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: SCV000630287.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Thr150Argfs*4) in the ACADM gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Thr150Argfs*4) 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). This variant is present in population databases (rs757500332, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with MCAD deficiency (PMID: 15915086, 19064330, 22796001, 25503862). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 189036). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Feb 28, 2020)
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criteria provided, single submitter
Method: clinical testing
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Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: yes
Allele origin:
germline
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Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital
Accession: SCV001739490.1
First in ClinVar: Jul 07, 2021 Last updated: Jul 07, 2021 |
Number of individuals with the variant: 1
Age: 0-9 years
Sex: male
Ethnicity/Population group: East asia
Geographic origin: China
Testing laboratory: Liwei's Lab
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Pathogenic
(Feb 22, 2018)
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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: SCV000220837.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 23, 2019 |
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Pathogenic
(Mar 17, 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: SCV002092829.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Pathogenic
(Apr 04, 2024)
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no assertion criteria provided
Method: literature only
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MCAD DEFICIENCY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV001786673.2
First in ClinVar: Aug 21, 2021 Last updated: Apr 15, 2024 |
Comment on evidence:
In a cohort of 31 Japanese patients with MCAD deficiency and 7 Japanese carriers of the disorder (ACADMD; 201450), Tajima et al. (2016) found that … (more)
In a cohort of 31 Japanese patients with MCAD deficiency and 7 Japanese carriers of the disorder (ACADMD; 201450), Tajima et al. (2016) found that the most prevalent mutation was a 4-bp deletion (c.449_452delCTGA) in the ACADM gene, predicted to result in a frameshift and premature termination (Thr150Argfs). The mutation, which was found by direct sequencing of the gene, was identified in 25 ACADM alleles of 22 individuals from 19 families. Analyses in patient lymphocytes showed that the mutation resulted in abolished ACADM enzyme activity. (less)
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Likely pathogenic
(-)
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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:
maternal
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Developmental and Behavioral Pediatrics, First Affiliated Hospital of Jilin University
Accession: SCV003838957.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Medium-chain acyl-coenzyme A dehydrogenase deficiency
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: SCV004800880.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
PVS1+PM2_P+PM3+PP4
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Han
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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Clinical, Biochemical, and Molecular Analyses of Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients. | Gong Z | Frontiers in genetics | 2021 | PMID: 33841490 |
Screening of MCAD deficiency in Japan: 16years' experience of enzymatic and genetic evaluation. | Tajima G | Molecular genetics and metabolism | 2016 | PMID: 27856190 |
Significance of ACADM mutations identified through newborn screening of MCAD deficiency in Japan. | Hara K | Molecular genetics and metabolism | 2016 | PMID: 26947917 |
First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China. | Liang C | Journal of pediatric endocrinology & metabolism : JPEM | 2015 | PMID: 25503862 |
Functional studies of 18 heterologously expressed medium-chain acyl-CoA dehydrogenase (MCAD) variants. | Koster KL | Journal of inherited metabolic disease | 2014 | PMID: 24966162 |
Clinical and molecular aspects of Japanese children with medium chain acyl-CoA dehydrogenase deficiency. | Purevsuren J | Molecular genetics and metabolism | 2012 | PMID: 22796001 |
MCAD deficiency in Denmark. | Andresen BS | Molecular genetics and metabolism | 2012 | PMID: 22542437 |
Clinical, biochemical and genetic analyses in two Korean patients with medium-chain acyl-CoA dehydrogenase deficiency. | Woo HI | The Korean journal of laboratory medicine | 2011 | PMID: 21239873 |
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 |
Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency. | Purevsuren J | Molecular genetics and metabolism | 2009 | PMID: 19699128 |
A novel molecular aspect of Japanese patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD): c.449-452delCTGA is a common mutation in Japanese patients with MCADD. | Purevsuren J | Molecular genetics and metabolism | 2009 | PMID: 19064330 |
Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency: under-representation of the common c.985 A > G mutation in the New York state population. | Nichols MJ | American journal of medical genetics. Part A | 2008 | PMID: 18241067 |
Medium-chain acyl-CoA dehydrogenase deficiency in gene-targeted mice. | Tolwani RJ | PLoS genetics | 2005 | PMID: 16121256 |
Genotypic differences of MCAD deficiency in the Asian population: novel genotype and clinical symptoms preceding newborn screening notification. | Ensenauer R | Genetics in medicine : official journal of the American College of Medical Genetics | 2005 | PMID: 15915086 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADM | - | - | - | - |
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Text-mined citations for rs786204642 ...
HelpRecord last updated Apr 15, 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.