This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ClinVar Genomic variation as it relates to human health
NM_000017.4(ACADS):c.625G>A (p.Gly209Ser)
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.
(15)
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.
Benign/Likely benign
15
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000017.4(ACADS):c.625G>A (p.Gly209Ser)
Variation ID: 3831 Accession: VCV000003831.48
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 12q24.31 12: 120738280 (GRCh38) [ NCBI UCSC ] 12: 121176083 (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 Apr 4, 2013 Oct 20, 2024 Feb 9, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000017.4:c.625G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000008.1:p.Gly209Ser missense NM_001302554.2:c.613G>A NP_001289483.1:p.Gly205Ser missense NC_000012.12:g.120738280G>A NC_000012.11:g.121176083G>A NG_007991.1:g.17513G>A P16219:p.Gly209Ser - Protein change
- G209S, G205S
- Other names
-
G185S
p.G209S:GGC>AGC
- Canonical SPDI
- NC_000012.12:120738279:G:A
-
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.
-
0.18231 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.18176
1000 Genomes Project 0.18231
The Genome Aggregation Database (gnomAD) 0.20617
Trans-Omics for Precision Medicine (TOPMed) 0.20679
Exome Aggregation Consortium (ExAC) 0.25918
The Genome Aggregation Database (gnomAD), exomes 0.26475
- 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. |
|||
| ACADS | - | - |
GRCh38 GRCh37 |
444 | 463 | |
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. |
|---|---|---|---|---|
| Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Nov 29, 2023 | RCV000004035.40 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 9, 2024 | RCV000077896.19 | |
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2023 | RCV000185685.26 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Apr 16, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000109725.8
First in ClinVar: Jan 17, 2014 Last updated: Jun 28, 2015 |
Number of individuals with the variant: 40
Sex: mixed
|
|
|
Likely benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001138838.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
|
Benign
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010900.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005218928.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Jan 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
inherited
|
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000746501.2
First in ClinVar: Dec 06, 2016 Last updated: Jun 17, 2019 |
Geographic origin: Iran
|
|
|
Benign
(Jan 04, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000238606.8
First in ClinVar: Jul 18, 2015 Last updated: Sep 27, 2019 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
|
Benign
(Dec 31, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000756747.5
First in ClinVar: May 03, 2018 Last updated: May 04, 2020 |
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000376683.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156791.7
First in ClinVar: Feb 09, 2020 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(Feb 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004813183.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
|
|
|
Benign
(Feb 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV003917249.13
First in ClinVar: Apr 23, 2023 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jan 01, 2001)
|
no assertion criteria provided
Method: literature only
|
SCAD DEFICIENCY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000024201.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Corydon et al. (2001) studied 10 patients with ethylmalonic aciduria and SCAD deficiency (201470) in fibroblasts and found a 625G-A change in the SCAD gene, … (more)
Corydon et al. (2001) studied 10 patients with ethylmalonic aciduria and SCAD deficiency (201470) in fibroblasts and found a 625G-A change in the SCAD gene, resulting in a gly185-to-ser (G185S) substitution, in 9 of the patients, 5 of whom were homozygous for this variation (3 had additional mutations). One patient with dysmorphic features and developmental delay was heterozygous for this mutation and for 511C-T (606885.0006), both of which have been referred to as 'variations,' because 14% of the general population has been found to be either homozygous or double heterozygous for them. Expression studies in E. coli showed that the G185S SCAD protein has 86% of wildtype activity. (less)
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Deficiency of butyryl-CoA dehydrogenase
Affected status: yes
Allele origin:
germline
|
GeneReviews
Accession: SCV000188414.3
First in ClinVar: Aug 15, 2014 Last updated: Oct 01, 2022 |
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Deficiency of butyryl-CoA dehydrogenase
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV000606903.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Premature birth (present) , Maternal teratogenic exposure (present) , Abnormal delivery (present) , Abnormality of the umbilical cord (present) , Abnormality of the placenta (present) … (more)
Premature birth (present) , Maternal teratogenic exposure (present) , Abnormal delivery (present) , Abnormality of the umbilical cord (present) , Abnormality of the placenta (present) , Prenatal maternal abnormality (present) , Decreased fetal movement (present) , Abnormality of the amniotic fluid (present) , Generalized hypotonia (present) , Abnormality of coordination (present) , Cognitive impairment (present) , Cerebral palsy (present) , Abnormality of digit (present) , Abnormality of the curvature of the vertebral column (present) , Abnormality of the musculature of the limbs (present) , Abnormality of muscle physiology (present) , Abnormality of the musculature of the thorax (present) , Abnormality of muscle morphology (present) , Abnormality of esophagus morphology (present) , Feeding difficulties (present) , Recurrent infections (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Method: Sanger Sequencing
Testing laboratory: GeneDx
Date variant was reported to submitter: 2015-10-02
Testing laboratory interpretation: Pathogenic
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Not Provided
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749956.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant interpreted as Benign and reported on 08-28-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report … (more)
Variant interpreted as Benign and reported on 08-28-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Autoimmunity (present) , Abnormality of the somatic nervous system (present) , Abnormality of the musculature of the limbs (present) , Hyperthyroidism (present) , Encephalopathy (present) … (more)
Autoimmunity (present) , Abnormality of the somatic nervous system (present) , Abnormality of the musculature of the limbs (present) , Hyperthyroidism (present) , Encephalopathy (present) , Generalized hypotonia (present) , Memory impairment (present) (less)
Indication for testing: Diagnostic
Age: 40-49 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2020-08-28
Testing laboratory interpretation: Benign
|
|
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Comment:
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Comment:
Variant interpreted as Benign and reported on 08-28-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
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:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Comment:
Variant interpreted as Benign and reported on 08-28-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Short-Chain Acyl-CoA Dehydrogenase Deficiency. | Adam MP | - | 2018 | PMID: 21938826 |
| Fasting and fat-loading tests provide pathophysiological insight into short-chain acyl-coenzyme a dehydrogenase deficiency. | van Maldegem BT | The Journal of pediatrics | 2010 | PMID: 19800078 |
| Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency. | Corydon MJ | Pediatric research | 2001 | PMID: 11134486 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADS | - | - | - | - |
Text-mined citations for rs1799958 ...
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 Nov 25, 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.