NM_000016.6(ACADM):c.536_568del (p.Lys179_Lys189del) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Feb 22, 2023
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:: RCV000673916.6

Allele description [Variation Report for NM_000016.6(ACADM):c.536_568del (p.Lys179_Lys189del)]

NM_000016.6(ACADM):c.536_568del (p.Lys179_Lys189del)

Gene:

ACADM:acyl-CoA dehydrogenase medium chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p31.1

Genomic location:

Preferred name:

NM_000016.6(ACADM):c.536_568del (p.Lys179_Lys189del)

HGVS:

NC_000001.11:g.75740047_75740079del
NG_007045.2:g.20690_20722del
NM_000016.6:c.536_568delMANE SELECT
NM_001127328.3:c.548_580del
NM_001286042.2:c.428_460del
NM_001286043.2:c.635_667del
NM_001286044.2:c.-32_1del
NP_000007.1:p.Lys179_Lys189del
NP_001120800.1:p.Lys183_Lys193del
NP_001272971.1:p.Lys143_Lys153del
NP_001272972.1:p.Lys212_Lys222del
NP_001272973.1:p.Met1del
LRG_838:g.20690_20722del
NC_000001.10:g.76205728_76205760del
NC_000001.10:g.76205732_76205764del
NM_000016.4:c.536_568del33

Protein change:

M1del

Links:

dbSNP: rs1553123869

NCBI 1000 Genomes Browser:

rs1553123869

Molecular consequence:

NM_000016.6:c.536_568del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001127328.3:c.548_580del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001286042.2:c.428_460del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001286043.2:c.635_667del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001286044.2:c.-32_1del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001286044.2:c.-32_1del - initiator_codon_variant - [Sequence Ontology: SO:0001582]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000799172	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Apr 11, 2018)	unknown	clinical testing	Citation Link,
SCV003231845	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 21, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23430840, 28492532
SCV004217355	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 22, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000799172

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Apr 11, 2018)

unknown

clinical testing

Citation Link,

SCV003231845

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 21, 2022)

germline

clinical testing

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

SCV004217355

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 22, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Relevance of expanded neonatal screening of medium-chain acyl co-a dehydrogenase deficiency: outcome of a decade in galicia (Spain).

Couce ML, Castiñeiras DE, Moure JD, Cocho JA, Sánchez-Pintos P, García-Villoria J, Quelhas D, Gregersen N, Andresen BS, Ribes A, Fraga JM.

JIMD Rep. 2011;1:131-6. doi: 10.1007/8904_2011_28. Epub 2011 Jun 25.

PubMed [citation]

PMID:: 23430840
PMCID:: PMC3509827

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000799172.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003231845.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ACADM protein in which other variant(s) (p.Asp181Gly) have been determined to be pathogenic (PMID: 23430840). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 557739). This variant has not been reported in the literature in individuals affected with ACADM-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.536_568del, results in the deletion of 11 amino acid(s) of the ACADM protein (p.Lys179_Lys189del), but otherwise preserves the integrity of the reading frame.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004217355.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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