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NM_000016.6(ACADM):c.127G>A (p.Glu43Lys) AND ACADM-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 31, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003415841.4

Allele description [Variation Report for NM_000016.6(ACADM):c.127G>A (p.Glu43Lys)]

NM_000016.6(ACADM):c.127G>A (p.Glu43Lys)

Gene:
ACADM:acyl-CoA dehydrogenase medium chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p31.1
Genomic location:
Preferred name:
NM_000016.6(ACADM):c.127G>A (p.Glu43Lys)
HGVS:
  • NC_000001.11:g.75732652G>A
  • NG_007045.2:g.13295G>A
  • NM_000016.6:c.127G>AMANE SELECT
  • NM_001127328.3:c.139G>A
  • NM_001286042.2:c.19G>A
  • NM_001286043.2:c.127G>A
  • NM_001286044.2:c.-259G>A
  • NP_000007.1:p.Glu43Lys
  • NP_000007.1:p.Glu43Lys
  • NP_001120800.1:p.Glu47Lys
  • NP_001272971.1:p.Glu7Lys
  • NP_001272972.1:p.Glu43Lys
  • NP_001272972.1:p.Glu43Lys
  • LRG_838t1:c.127G>A
  • LRG_838:g.13295G>A
  • LRG_838p1:p.Glu43Lys
  • NC_000001.10:g.76198337G>A
  • NM_000016.4:c.127G>A
  • NM_000016.5:c.127G>A
  • NM_001286043.1:c.127G>A
Protein change:
E43K
Links:
dbSNP: rs147559466
NCBI 1000 Genomes Browser:
rs147559466
Molecular consequence:
  • NM_001286044.2:c.-259G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000016.6:c.127G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127328.3:c.139G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001286042.2:c.19G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001286043.2:c.127G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
ACADM-related disorder
Synonyms:
ACADM-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004109177PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 31, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004109177.1

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

Description

The ACADM c.127G>A variant is predicted to result in the amino acid substitution p.Glu43Lys. The c.127G>A variant has been reported in a large population database at an allele frequency of up to 0.44%, which is relatively high for a pathogenic variant (http://gnomad.broadinstitute.org/variant/1-76198337-G-A). It has also been reported in patients with suspected medium chain acyl-CoA dehydrogenase deficiency (MCADD), though it is unclear whether the c.127G>A variant causes a mild biochemical phenotype or is an innocuous, benign variant (McKinney et al 2004. PubMed ID: 15171998; Sturm et al. 2012. PubMed ID: 23028790; Koster et al. 2014. PubMed ID: 24966162). It has been observed in individuals with the common c.985A>G (p.Lys304Glu) variant (Smith EH et al 2010. PubMed ID: 20434380), although it should be noted that the c.985A>G variant in the heterozygous state alone may lead to a false positive newborn screen suggestive of MCADD (Merritt and Chang. 2019. PubMed ID: 20301597). We have observed the c.127G>A variant internally in approximately a dozen individuals with suspected MCADD, many identified based on abnormal newborn screen results. In two individuals, we found no second ACADM variant whereas eight individuals were found to be heterozygous for both the c.127G>A variant and the common c.985A>G variant. The c.127G>A variant is listed in the ClinVar database with interpretations of pathogenic, uncertain significance, and likely benign (www.ncbi.nlm.nih.gov/clinvar/variation/92257). In summary, the clinical significance of this variant is currently uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: Sep 16, 2024