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NM_000017.4(ACADS):c.1054G>A (p.Ala352Thr) AND Deficiency of butyryl-CoA dehydrogenase

Germline classification:
Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:
Jan 4, 2024
Review status:
criteria provided, conflicting classifications
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000673648.13

Allele description [Variation Report for NM_000017.4(ACADS):c.1054G>A (p.Ala352Thr)]

NM_000017.4(ACADS):c.1054G>A (p.Ala352Thr)

Gene:
ACADS:acyl-CoA dehydrogenase short chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.31
Genomic location:
Preferred name:
NM_000017.4(ACADS):c.1054G>A (p.Ala352Thr)
HGVS:
  • NC_000012.12:g.120739164G>A
  • NG_007991.1:g.18397G>A
  • NM_000017.4:c.1054G>AMANE SELECT
  • NM_001302554.2:c.1042G>A
  • NP_000008.1:p.Ala352Thr
  • NP_001289483.1:p.Ala348Thr
  • NC_000012.11:g.121176967G>A
  • NM_000017.2:c.1054G>A
Protein change:
A348T
Links:
dbSNP: rs202078273
NCBI 1000 Genomes Browser:
rs202078273
Molecular consequence:
  • NM_000017.4:c.1054G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001302554.2:c.1042G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Deficiency of butyryl-CoA dehydrogenase (ACADSD)
Synonyms:
ACYL-CoA DEHYDROGENASE, SHORT-CHAIN, DEFICIENCY OF; Lipid-storage myopathy secondary to short chain acyl CoA dehydrogenase deficiency; SCAD DEFICIENCY, MILD
Identifiers:
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)
OriginMethodCitations
SCV000798875Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))
Uncertain significance
(Mar 27, 2018)
unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001543730Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jan 4, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002033271Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Nov 7, 2021)
germlineclinical testing

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

SCV002783195Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Aug 30, 2021)
unknownclinical testing

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

SCV004800891Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital
no assertion criteria provided

(ACMG Guidelines, 2015)
Pathogenicgermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
Donggermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

Mitochondrial fatty acid oxidation defects--remaining challenges.

Gregersen N, Andresen BS, Pedersen CB, Olsen RK, Corydon TJ, Bross P.

J Inherit Metab Dis. 2008 Oct;31(5):643-57. doi: 10.1007/s10545-008-0990-y. Epub 2008 Oct 7.

PubMed [citation]
PMID:
18836889

Clinical relevance of short-chain acyl-CoA dehydrogenase (SCAD) deficiency: Exploring the role of new variants including the first SCAD-disease-causing allele carrying a synonymous mutation.

Tonin R, Caciotti A, Funghini S, Pasquini E, Mooney SD, Cai B, Proncopio E, Donati MA, Baronio F, Bettocchi I, Cassio A, Biasucci G, Bordugo A, la Marca G, Guerrini R, Morrone A.

BBA Clin. 2016 Jun;5:114-9. doi: 10.1016/j.bbacli.2016.03.004.

PubMed [citation]
PMID:
27051597
PMCID:
PMC4816031
See all PubMed Citations (5)
PMC

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Details of each submission

From Counsyl, SCV000798875.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001543730.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 352 of the ACADS protein (p.Ala352Thr). This variant is present in population databases (rs202078273, gnomAD 0.004%). This missense change has been observed in individuals with biochemical features of short chain acyl-CoA dehydrogenase (SCAD) deficiency (PMID: 27051597, 30612563). ClinVar contains an entry for this variant (Variation ID: 432218). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADS protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

From Genome-Nilou Lab, SCV002033271.1

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

From Fulgent Genetics, Fulgent Genetics, SCV002783195.1

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

From Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital, SCV004800891.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Dong1not providednot providedclinical testingnot provided

Description

PM2_P+PM3_VS+PP3+PP4

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024