VCV000003833.35 - ClinVar

NM_000017.4(ACADS):c.307GAG[1] (p.Glu104del)

Germline

Classification

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.

(8)

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

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.307GAG[1] (p.Glu104del)

Variation ID: 3833 Accession: VCV000003833.35

Type and length

Microsatellite, 3 bp

Location

Cytogenetic: 12q24.31 12: 120737081-120737083 (GRCh38) [ NCBI UCSC ] 12: 121174884-121174886 (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	May 17, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000017.4:c.307GAG[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000008.1:p.Glu104del	inframe deletion
NM_000017.4:c.310_312del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000017.2:c.310_312delGAG
NM_001302554.2:c.307GAG[1]	NP_001289483.1:p.Glu104del	inframe deletion
NC_000012.12:g.120737082GAG[1]
NC_000012.11:g.121174885GAG[1]
NG_007991.1:g.16315GAG[1]
NG_007991.1:g.16318_16320del

... more HGVS ... less HGVS

Protein change

E104del

Other names

Canonical SPDI

NC_000012.12:120737080:GGAGGAG:GGAG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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

ClinGen: CA252884 OMIM: 606885.0009 dbSNP: rs387906308 VarSome

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
Gene	OMIM	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.
Deficiency of butyryl-CoA dehydrogenase	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	May 17, 2023	RCV000004037.20
not provided	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Nov 3, 2021	RCV000185702.29

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.
Pathogenic (Feb 20, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Deficiency of butyryl-CoA dehydrogenase Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001367103.2 First in ClinVar: Jul 06, 2020 Last updated: Dec 12, 2020	Comment: This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PS3,PM3.
Pathogenic (Nov 03, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) 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: SCV002010901.3 First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023
Pathogenic (Apr 02, 2014)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000238623.2 First in ClinVar: Jul 18, 2015 Last updated: Jul 18, 2015	Comment: The c.310_312delGAG mutation in the ACADS gene has been reported previously in association with short chain acyl-CoA dehydrogenase (SCAD) deficiency in an individual who also … (more) The c.310_312delGAG mutation in the ACADS gene has been reported previously in association with short chain acyl-CoA dehydrogenase (SCAD) deficiency in an individual who also harbored the common G209S variant and in whom fibroblast SCAD activity was undetectable (Corydon et al., 2001). The deletion results in the loss of a single Glutamic Acid at codon 104, denoted p.Glu104del. The surrounding sequence GGAG{delGAG}ATCA. The variant is found in ACADS panel(s). (less)
Pathogenic (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Deficiency of butyryl-CoA dehydrogenase Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002816828.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (May 17, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Deficiency of butyryl-CoA dehydrogenase Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000632501.3 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024	Publications: PubMed (3) PubMed: 11134486‚ 26110041‚ 29678161 Comment: Experimental studies have shown that this variant affects ACADS function (PMID: 11134486). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to … (more) Experimental studies have shown that this variant affects ACADS function (PMID: 11134486). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 3833). This variant has been observed in individuals with short-chain acyl-CoA dehydrogenase deficiency (PMID: 11134486, 26110041, 29678161). This variant is present in population databases (rs751780151, gnomAD 0.003%). This variant, c.310_312del, results in the deletion of 1 amino acid(s) of the ACADS protein (p.Glu104del), but otherwise preserves the integrity of the reading frame. (less)
Pathogenic (Mar 01, 2018)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001248112.26 First in ClinVar: May 12, 2020 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: SCV000024203.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (1) PubMed: 11134486 Comment on evidence: In a boy with SCAD deficiency (201470) who was noted in the neonatal period to have hypotonia and later developmental delay, Corydon et al. (2001) … (more) In a boy with SCAD deficiency (201470) who was noted in the neonatal period to have hypotonia and later developmental delay, Corydon et al. (2001) identified a heterozygous 3-bp deletion (310-312delGAG) in the SCAD gene, resulting in the deletion of a glutamic acid residue at amino acid 80. Expression studies in E. coli for this allele showed undetectable activity. The patient was also heterozygous for the 625A allele (606885.0007). (less)
Pathogenic (Jan 24, 2019)	no assertion criteria provided Method: clinical testing	Deficiency of butyryl-CoA dehydrogenase Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV001132114.1 First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019	Publications: PubMed (3) PubMed: 11134486‚ 29678161‚ 26110041

Comment:

The c.310_312delGAG mutation in the ACADS gene has been reported previously in association with short chain acyl-CoA dehydrogenase (SCAD) deficiency in an individual who also harbored the common G209S variant and in whom fibroblast SCAD activity was undetectable (Corydon et al., 2001). The deletion results in the loss of a single Glutamic Acid at codon 104, denoted p.Glu104del. The surrounding sequence GGAG{delGAG}ATCA. The variant is found in ACADS panel(s).

Comment:

Experimental studies have shown that this variant affects ACADS function (PMID: 11134486). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 3833). This variant has been observed in individuals with short-chain acyl-CoA dehydrogenase deficiency (PMID: 11134486, 26110041, 29678161). This variant is present in population databases (rs751780151, gnomAD 0.003%). This variant, c.310_312del, results in the deletion of 1 amino acid(s) of the ACADS protein (p.Glu104del), but otherwise preserves the integrity of the reading frame.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
An unusually high frequency of SCAD deficiency caused by two pathogenic variants in the ACADS gene and its relationship to the ethnic structure in Slovakia.	Lisyová J	BMC medical genetics	2018	PMID: 29678161
A case report of short-chain acyl-CoA dehydrogenase deficiency (SCADD).	Lampret BR	Biochemia medica	2015	PMID: 26110041
Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency.	Corydon MJ	Pediatric research	2001	PMID: 11134486

Text-mined citations for rs387906308 ...

These 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

ClinVar Genomic variation as it relates to human health

NM_000017.4(ACADS):c.307GAG[1] (p.Glu104del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs387906308 ...