NM_000016.6(ACADM):c.1150G>T (p.Glu384Ter) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 2, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000411952.9

Allele description [Variation Report for NM_000016.6(ACADM):c.1150G>T (p.Glu384Ter)]

NM_000016.6(ACADM):c.1150G>T (p.Glu384Ter)

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.1150G>T (p.Glu384Ter)

HGVS:

NC_000001.11:g.75761326G>T
NG_007045.2:g.41969G>T
NM_000016.6:c.1150G>TMANE SELECT
NM_001127328.3:c.1162G>T
NM_001286042.2:c.1042G>T
NM_001286043.2:c.1249G>T
NM_001286044.2:c.583G>T
NP_000007.1:p.Glu384Ter
NP_000007.1:p.Glu384Ter
NP_001120800.1:p.Glu388Ter
NP_001272971.1:p.Glu348Ter
NP_001272972.1:p.Glu417Ter
NP_001272973.1:p.Glu195Ter
LRG_838t1:c.1150G>T
LRG_838:g.41969G>T
LRG_838p1:p.Glu384Ter
NC_000001.10:g.76227011G>T
NM_000016.4:c.1150G>T
NM_000016.5:c.1150G>T

Protein change:

E195*

Links:

dbSNP: rs748110745

NCBI 1000 Genomes Browser:

rs748110745

Molecular consequence:

NM_000016.6:c.1150G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127328.3:c.1162G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001286042.2:c.1042G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001286043.2:c.1249G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001286044.2:c.583G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000486618	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jul 8, 2016)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV001206380	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 2, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 8198141, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000486618

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Jul 8, 2016)

unknown

clinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001206380

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 2, 2023)

germline

clinical testing

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

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

Disease-causing mutations in exon 11 of the medium-chain acyl-CoA dehydrogenase gene.

Andresen BS, Jensen TG, Bross P, Knudsen I, Winter V, Kølvraa S, Bolund L, Ding JH, Chen YT, Van Hove JL, et al.

Am J Hum Genet. 1994 Jun;54(6):975-88.

PubMed [citation]

PMID:: 8198141
PMCID:: PMC1918184

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

Details of each submission

From Counsyl, SCV000486618.2

#	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 Invitae, SCV001206380.5

#	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 creates a premature translational stop signal (p.Glu384*) in the ACADM gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the ACADM protein. This variant is present in population databases (rs748110745, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with MCAD deficiency (PMID: 8198141). ClinVar contains an entry for this variant (Variation ID: 371122). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects ACADM function (PMID: 8198141). For these reasons, this variant has been classified as 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

Last Updated: Feb 20, 2024

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