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NM_000016.6(ACADM):c.50G>A (p.Arg17His) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Germline classification:
Conflicting interpretations of pathogenicity (6 submissions)
Last evaluated:
Feb 15, 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:
RCV000211437.17

Allele description [Variation Report for NM_000016.6(ACADM):c.50G>A (p.Arg17His)]

NM_000016.6(ACADM):c.50G>A (p.Arg17His)

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.50G>A (p.Arg17His)
HGVS:
  • NC_000001.11:g.75728420G>A
  • NG_007045.2:g.9063G>A
  • NM_000016.6:c.50G>AMANE SELECT
  • NM_001127328.3:c.62G>A
  • NM_001286042.2:c.10+3603G>A
  • NM_001286043.2:c.50G>A
  • NM_001286044.2:c.-268+3603G>A
  • NP_000007.1:p.Arg17His
  • NP_001120800.1:p.Arg21His
  • NP_001272972.1:p.Arg17His
  • LRG_838:g.9063G>A
  • NC_000001.10:g.76194105G>A
  • NM_000016.4:c.50G>A
Protein change:
R17H
Links:
dbSNP: rs17848070
NCBI 1000 Genomes Browser:
rs17848070
Molecular consequence:
  • NM_001286042.2:c.10+3603G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001286044.2:c.-268+3603G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000016.6:c.50G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127328.3:c.62G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001286043.2:c.50G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Medium-chain acyl-coenzyme A dehydrogenase deficiency (ACADMD)
Synonyms:
CARNITINE DEFICIENCY SECONDARY TO MEDIUM-CHAIN ACYL-CoA DEHYDROGENASE DEFICIENCY; MCADD; Medium chain acyl-CoA dehydrogenase deficiency
Identifiers:
MONDO: MONDO:0008721; MedGen: C0220710; Orphanet: 42; OMIM: 201450

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000268463ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Feb 20, 2015)
germlineclinical testing

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

SCV002580157MGZ Medical Genetics Center
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Aug 19, 2022)
germlineclinical testing

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

SCV002776945Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Jul 7, 2021)
unknownclinical testing

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

SCV003489451Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 25, 2022)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV003838956Developmental and Behavioral Pediatrics, First Affiliated Hospital of Jilin University
no assertion criteria provided
Likely pathogenicpaternalclinical testing

SCV004212169Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Feb 15, 2024)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedpaternalunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Dissection of biochemical borderline phenotypes in carriers and genetic variants of medium-chain acyl-CoA dehyrogenase deficiency: implications for newborn screening [corrected].

Maier EM, Pongratz J, Muntau AC, Liebl B, Nennstiel-Ratzel U, Busch U, Fingerhut R, Olgemöller B, Roscher AA, Röschinger W.

Clin Genet. 2009 Aug;76(2):179-87. doi: 10.1111/j.1399-0004.2009.01217.x. Erratum in: Clin Genet. 2010 Mar;77(3):304.

PubMed [citation]
PMID:
19780764

Significance of ACADM mutations identified through newborn screening of MCAD deficiency in Japan.

Hara K, Tajima G, Okada S, Tsumura M, Kagawa R, Shirao K, Ohno Y, Yasunaga S, Ohtsubo M, Hata I, Sakura N, Shigematsu Y, Takihara Y, Kobayashi M.

Mol Genet Metab. 2016 May;118(1):9-14. doi: 10.1016/j.ymgme.2015.12.011. Epub 2015 Dec 29.

PubMed [citation]
PMID:
26947917
See all PubMed Citations (5)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000268463.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing
(GTR000500814.1)
PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided
(GTR000500814.1)
1not providednot providednot provided

From MGZ Medical Genetics Center, SCV002580157.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Fulgent Genetics, Fulgent Genetics, SCV002776945.1

#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 Invitae, SCV003489451.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 17 of the ACADM protein (p.Arg17His). This variant is present in population databases (rs17848070, gnomAD 0.01%). This missense change has been observed in individual(s) with a positive newborn screening result for ACADM-related disease (PMID: 19780764, 26947917, 27856190). ClinVar contains an entry for this variant (Variation ID: 226078). 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 not expected to disrupt ACADM protein function. Experimental studies have shown that this missense change affects ACADM function (PMID: 27856190). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Developmental and Behavioral Pediatrics, First Affiliated Hospital of Jilin University, SCV003838956.1

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

From Baylor Genetics, SCV004212169.2

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

Last Updated: Jun 17, 2024