NM_000017.4(ACADS):c.164C>T (p.Pro55Leu) AND Deficiency of butyryl-CoA dehydrogenase

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 14, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:

Allele description [Variation Report for NM_000017.4(ACADS):c.164C>T (p.Pro55Leu)]

NM_000017.4(ACADS):c.164C>T (p.Pro55Leu)

ACADS:acyl-CoA dehydrogenase short chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000017.4(ACADS):c.164C>T (p.Pro55Leu)
  • NC_000012.12:g.120727143C>T
  • NG_007991.1:g.6376C>T
  • NM_000017.4:c.164C>TMANE SELECT
  • NM_001302554.2:c.164C>T
  • NP_000008.1:p.Pro55Leu
  • NP_001289483.1:p.Pro55Leu
  • NC_000012.11:g.121164946C>T
  • NM_000017.2:c.164C>T
Protein change:
OMIM: 606885.0014; dbSNP: rs147442301
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000017.4:c.164C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001302554.2:c.164C>T - missense variant - [Sequence Ontology: SO:0001583]


Deficiency of butyryl-CoA dehydrogenase (ACADSD)
ACYL-CoA DEHYDROGENASE, SHORT-CHAIN, DEFICIENCY OF; Lipid-storage myopathy secondary to short chain acyl CoA dehydrogenase deficiency; SCAD DEFICIENCY, MILD
MONDO: MONDO:0008722; MedGen: C0342783; Orphanet: 26792; OMIM: 201470

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000044876OMIMno assertion criteria providedPathogenic
(Jun 1, 2010)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000793186Counsylcriteria provided, single submitter
Likely pathogenic
(Jul 31, 2017)
unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV000914564Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
(Aug 14, 2018)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Targeted Next-Generation Sequencing for Clinical Diagnosis of 561 Mendelian Diseases.

Liu Y, Wei X, Kong X, Guo X, Sun Y, Man J, Du L, Zhu H, Qu Z, Tian P, Mao B, Yang Y.

PLoS One. 2015;10(8):e0133636. doi: 10.1371/journal.pone.0133636. Erratum in: PLoS One. 2015;10(9):e0139258. PLoS One. 2016;11(1):e0148154.

PubMed [citation]

Novel and Recurrent ACADS Mutations and Clinical Manifestations Observed in Korean Patients with Short-chain Acyl-coenzyme a Dehydrogenase Deficiency.

Kim YM, Cheon CK, Park KH, Park S, Kim GH, Yoo HW, Lee KA, Ko JM.

Ann Clin Lab Sci. 2016 Jul;46(4):360-6.

PubMed [citation]
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000044876.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In 2 unrelated Japanese girls with biochemical evidence of SCAD deficiency (201470) but without clinical manifestations, Shirao et al. (2010) identified compound heterozygosity for mutations in the ACADS gene. Both girls carried a 164C-T transition in exon 2, resulting in a pro55-to-leu (P55L) substitution, and 1 girl had a 1031A-G transition in exon 9, resulting in a glu344-to-gly (E344G; 606885.0015) substitution, and the other girl had a 323G-A transition in exon 3, resulting in a gly108-to-asp (G108D; 606880.0016) substitution. In vitro functional expression studies in HEK293 and human osteosarcoma cells showed that each of the 3 mutant proteins had less than 10% residual enzyme activity, were retained in the insoluble fraction of the cell consistent with abnormal aggregation, and caused increased mitochondrial fragmentation associated with autophagy. Despite the functional evidence of mutant ACADS dysfunction, neither girl showed symptoms at age 4 years; Shirao et al. (2010) noted that the genotype/phenotype correlation was unclear.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000793186.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000914564.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)


The ACADS c.164C>T (p.Pro55Leu) missense variant has been reported in four studies in which it is found in a total of six individuals with SCAD deficiency, including in one with the variant in a homozygous state and in five in a compound heterozygous state. All individuals carrying the variant were diagnosed with SCAD deficiency through newborn screening and were clinically asymptomatic, even during follow-up in childhood (Jethva and Ficicioqlu 2008; Shirao et al. 2010; An et al. 2016; Kim et al. 2016). In addition, Huang et al. (2016) reported the p.Pro55Leu variant in approximately 20% of 17 clinically asymptomatic Chinese children who were identified through newborn screening as having SCAD deficiency. Control data are unavailable for this variant, which is reported at a frequency of 0.00092 in the East Asian population of the Exome Aggregation Consortium. Shirao et al. (2010) performed in vitro testing of the variant and found that HEK293 cells that were transfected with the variant protein had 6.67% enzymatic activity compared to wild type. When the variant was co-transfected with wild type protein, 60-70% of normal enzymatic activity was observed. Based on the collective evidence, the p.Pro55Leu variant is classified as pathogenic for SCAD deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2020

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