For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has been observed in individual(s) with MCAD deficiency (PMID: 20434380, 21083904, 23028790, 31012112). This variant is present in population databases (rs756277519, gnomAD 0.0009%). This variant, c.430_432del, results in the deletion of 1 amino acid(s) of the ACADM protein (p.Lys144del), but otherwise preserves the integrity of the reading frame.
ClinVar Genomic variation as it relates to human health
NM_000016.6(ACADM):c.424AAG[2] (p.Lys144del)
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
-
NM_000016.6(ACADM):c.424AAG[2] (p.Lys144del)
Variation ID: 226062 Accession: VCV000226062.23
- Type and length
-
Microsatellite, 3 bp
- Location
-
Cytogenetic: 1p31.1 1: 75734827-75734829 (GRCh38) [ NCBI UCSC ] 1: 76200512-76200514 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 29, 2024 Apr 2, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000016.6:c.424AAG[2] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000007.1:p.Lys144del inframe deletion NM_000016.6:c.430_432del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000016.4:c.430_432del NM_000016.4:c.430_432delAAG NM_001127328.3:c.436AAG[2] NP_001120800.1:p.Lys148del inframe deletion NM_001286042.2:c.316AAG[2] NP_001272971.1:p.Lys108del inframe deletion NM_001286043.2:c.523AAG[2] NP_001272972.1:p.Lys177del inframe deletion NM_001286044.2:c.-100+1905AAG[2] intron variant NC_000001.11:g.75734827AAG[2] NC_000001.10:g.76200512AAG[2] NG_007045.2:g.15470AAG[2] LRG_838:g.15470AAG[2] - Protein change
- K144del, K148del, K177del, K108del
- Other names
- -
- Canonical SPDI
- NC_000001.11:75734826:AAGAAGAAG:AAGAAG
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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 (5) |
criteria provided, multiple submitters, no conflicts
|
Mar 11, 2024 | RCV000211510.17 | |
| Likely pathogenic (2) |
criteria provided, single submitter
|
Apr 2, 2024 | RCV000313722.10 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Feb 20, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
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: SCV000268445.1
First in ClinVar: May 21, 2016 Last updated: May 21, 2016 |
|
|
|
Pathogenic
(May 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001578471.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has been observed in individual(s) with MCAD deficiency (PMID: 20434380, 21083904, 23028790, 31012112). This variant is present in population databases (rs756277519, gnomAD 0.0009%). This variant, c.430_432del, results in the deletion of 1 amino acid(s) of the ACADM protein (p.Lys144del), but otherwise preserves the integrity of the reading frame. (less)
|
|
|
Likely pathogenic
(Apr 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001817954.2
First in ClinVar: Sep 08, 2021 Last updated: Sep 29, 2024 |
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports … (more)
In-frame deletion of 1 amino acid in a non-repeat region; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23028790, 21083904, 20434380, 27308838, 31012112, 25940036) (less)
|
|
|
Likely pathogenic
(May 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: yes
Allele origin:
germline
|
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV004013930.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
PM1, PM2, PM4, PP3, PP5
|
|
|
Likely pathogenic
(Mar 11, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004210669.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Likely pathogenic
(Mar 07, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Medium-chain acyl-coenzyme A dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV001132317.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
|
|
|
Uncertain significance
(Oct 02, 2015)
|
Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000330908.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 2
Sex: mixed
|
|
| Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more | |||||
Comment:
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23028790, 21083904, 20434380, 27308838, 31012112, 25940036)
Comment:
PM1, PM2, PM4, PP3, PP5
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:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has been observed in individual(s) with MCAD deficiency (PMID: 20434380, 21083904, 23028790, 31012112). This variant is present in population databases (rs756277519, gnomAD 0.0009%). This variant, c.430_432del, results in the deletion of 1 amino acid(s) of the ACADM protein (p.Lys144del), but otherwise preserves the integrity of the reading frame.
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23028790, 21083904, 20434380, 27308838, 31012112, 25940036)
Comment:
PM1, PM2, PM4, PP3, PP5
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A nationwide retrospective observational study of population newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in the Netherlands. | Jager EA | Journal of inherited metabolic disease | 2019 | PMID: 31012112 |
| Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing. | Narravula A | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27308838 |
| Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening. | Gramer G | JIMD reports | 2015 | PMID: 25940036 |
| Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants. | Sturm M | PloS one | 2012 | PMID: 23028790 |
| 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 |
| 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 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADM | - | - | - | - |
Text-mined citations for rs875989857 ...
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 Oct 08, 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.