NM_000016.6(ACADM):c.424AAG[2] (p.Lys144del) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 30, 2020)

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:
RCV000211510.4

Allele description [Variation Report for NM_000016.6(ACADM):c.424AAG[2] (p.Lys144del)]

NM_000016.6(ACADM):c.424AAG[2] (p.Lys144del)

Gene:
ACADM:acyl-CoA dehydrogenase medium chain [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
1p31.1
Genomic location:
Preferred name:
NM_000016.6(ACADM):c.424AAG[2] (p.Lys144del)
HGVS:
  • NC_000001.11:g.75734827AAG[2]
  • NG_007045.2:g.15470AAG[2]
  • NM_000016.6:c.424AAG[2]MANE SELECT
  • NM_001127328.3:c.436AAG[2]
  • NM_001286042.2:c.316AAG[2]
  • NM_001286043.2:c.523AAG[2]
  • NM_001286044.2:c.-100+1905AAG[2]
  • NP_000007.1:p.Lys144del
  • NP_001120800.1:p.Lys148del
  • NP_001272971.1:p.Lys108del
  • NP_001272972.1:p.Lys177del
  • LRG_838:g.15470AAG[2]
  • NC_000001.10:g.76200512AAG[2]
  • NC_000001.10:g.76200512_76200514del
  • NM_000016.4:c.430_432delAAG
Protein change:
K108del
Links:
dbSNP: rs875989857
NCBI 1000 Genomes Browser:
rs875989857
Molecular consequence:
  • NM_000016.6:c.424AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001127328.3:c.436AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001286042.2:c.316AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001286043.2:c.523AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001286044.2:c.-100+1905AAG[2] - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000268445ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Feb 20, 2015)
germlineclinical testing

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

SCV001132317Counsylno assertion criteria providedLikely pathogenic
(Mar 7, 2017)
unknownclinical testing

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

SCV001578471Invitaecriteria provided, single submitter
Pathogenic
(Aug 30, 2020)
germlineclinical testing

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

Summary from all submissions

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

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing.

Narravula A, Garber KB, Askree SH, Hegde M, Hall PL.

Genet Med. 2017 Jan;19(1):77-82. doi: 10.1038/gim.2016.67. Epub 2016 Jun 16.

PubMed [citation]
PMID:
27308838
See all PubMed Citations (8)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000268445.1

#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 Counsyl, SCV001132317.1

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

From Invitae, SCV001578471.1

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

Description

This variant, c.430_432del, results in the deletion of 1 amino acid(s) of the ACADM protein (p.Lys144del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs756277519, ExAC 0.002%). This variant has been observed in individual(s) with MCAD deficiency (PMID: 21083904, 31012112, 23028790, 20434380). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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