NM_000016.6(ACADM):c.388-19T>A AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 14, 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:: RCV000667810.6

Allele description [Variation Report for NM_000016.6(ACADM):c.388-19T>A]

NM_000016.6(ACADM):c.388-19T>A

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.388-19T>A

HGVS:

NC_000001.11:g.75734772T>A
NG_007045.2:g.15415T>A
NM_000016.6:c.388-19T>AMANE SELECT
NM_001127328.3:c.400-19T>A
NM_001286042.2:c.280-19T>A
NM_001286043.2:c.487-19T>A
NM_001286044.2:c.-100+1850T>A
LRG_838:g.15415T>A
NC_000001.10:g.76200457T>A
NM_000016.4:c.388-19T>A

Links:

dbSNP: rs1553123252

NCBI 1000 Genomes Browser:

rs1553123252

Molecular consequence:

NM_000016.6:c.388-19T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001127328.3:c.400-19T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001286042.2:c.280-19T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001286043.2:c.487-19T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001286044.2:c.-100+1850T>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000792315	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jun 14, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV003522760	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 29, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22542437, 28492532
SCV005056979	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 14, 2024)	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

SCV000792315

Counsyl

criteria provided, single submitter

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

Uncertain significance
(Jun 14, 2017)

unknown

clinical testing

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

Citation Link,

SCV003522760

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 29, 2023)

germline

clinical testing

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

SCV005056979

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 14, 2024)

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

MCAD deficiency in Denmark.

Andresen BS, Lund AM, Hougaard DM, Christensen E, Gahrn B, Christensen M, Bross P, Vested A, Simonsen H, Skogstrand K, Olpin S, Brandt NJ, Skovby F, Nørgaard-Pedersen B, Gregersen N.

Mol Genet Metab. 2012 Jun;106(2):175-88. doi: 10.1016/j.ymgme.2012.03.018. Epub 2012 Apr 4.

PubMed [citation]

PMID:: 22542437

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, SCV000792315.1

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003522760.2

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

Description

This sequence change falls in intron 5 of the ACADM gene. It does not directly change the encoded amino acid sequence of the ACADM protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with medium-chain acyl-CoA dehydrogenase deficiency (MCADD) (PMID: 22542437). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552529). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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, SCV005056979.1

#	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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Relating variation to medicine