NM_000017.4(ACADS):c.1058C>T (p.Ser353Leu) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Dec 12, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000185693.4

Allele description [Variation Report for NM_000017.4(ACADS):c.1058C>T (p.Ser353Leu)]

NM_000017.4(ACADS):c.1058C>T (p.Ser353Leu)

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.1058C>T (p.Ser353Leu)
Other names:
S329L; p.S353L:TCG>TTG
HGVS:
  • NC_000012.12:g.120739168C>T
  • NG_007991.1:g.18401C>T
  • NM_000017.4:c.1058C>TMANE SELECT
  • NM_001302554.2:c.1046C>T
  • NP_000008.1:p.Ser353Leu
  • NP_001289483.1:p.Ser349Leu
  • NC_000012.11:g.121176971C>T
  • NM_000017.2:c.1058C>T
  • NM_000017.3:c.1058C>T
  • P16219:p.Ser353Leu
Protein change:
S349L; SER329LEU
Links:
UniProtKB: P16219#VAR_013570; OMIM: 606885.0012; dbSNP: rs28941773
NCBI 1000 Genomes Browser:
rs28941773
Molecular consequence:
  • NM_000017.4:c.1058C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001302554.2:c.1046C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000238614GeneDxcriteria provided, single submitter
Likely pathogenic
(Jan 12, 2017)
germlineclinical testing

Citation Link,

SCV000883331ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Dec 12, 2017)
germlineclinical testing

Citation Link,

SCV001148848CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Likely pathogenic
(Jun 1, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000238614.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The S353L missense variant in the ACADS gene has been reported previously as S329L in a patient with 10% of control short chain acyl-CoA dehydrogenase (SCAD) enzyme activity in fibroblasts who harbored the G209S reportable variant on the opposite ACADS allele (Corydon et al., 2001). Expression of S353L in E. coli found that is associated with undetectable SCAD enzyme activity compared to wild-type (Corydon et al., 2001). Therefore, we interpret S353L to be a likely pathogenic variant.

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

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000883331.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ACADS p.Ser353Leu variant (rs28941773) has been reported in two individuals with a diagnosis of short-chain acyl-CoA dehydrogenase (SCAD) deficiency who also had a common risk factor variant (Corydon 2001 and Dessein 2017). Furthermore, functional studies show that the ACADS protein harboring the p.Ser353Leu variant does not have detectable enzymatic activity compared to wild type when expressed in bacteria (Corydon 2001). The p.Ser353Leu variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.044% in the non-Finnish European population (identified in 54 out of 123,600 chromosomes), which is consistent with a recessive carrier frequency. This variant is also present in the ClinVar database (Variant ID: 3836). Therefore, based on the available evidence, the p.Ser353Leu variant is classified as likely pathogenic.

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

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001148848.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 6, 2021

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