NM_000016.6(ACADM):c.1A>G (p.Met1Val) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 21, 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:: RCV000411404.7

Allele description [Variation Report for NM_000016.6(ACADM):c.1A>G (p.Met1Val)]

NM_000016.6(ACADM):c.1A>G (p.Met1Val)

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.1A>G (p.Met1Val)

HGVS:

NC_000001.11:g.75724788A>G
NG_007045.2:g.5431A>G
NM_000016.6:c.1A>GMANE SELECT
NM_001127328.3:c.1A>G
NM_001286042.2:c.-20A>G
NM_001286043.2:c.1A>G
NM_001286044.2:c.-297A>G
NP_000007.1:p.Met1Val
NP_001120800.1:p.Met1Val
NP_001272972.1:p.Met1Val
LRG_838:g.5431A>G
NC_000001.10:g.76190473A>G
NC_000001.10:g.76190473A>G
NM_000016.4:c.1A>G

Protein change:

M1V

Links:

dbSNP: rs1057516778

NCBI 1000 Genomes Browser:

rs1057516778

Molecular consequence:

NM_001286042.2:c.-20A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001286044.2:c.-297A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000016.6:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001127328.3:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001286043.2:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000016.6:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127328.3:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286043.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

effect on translation [Variation Ontology: 0399]

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
SCV000486211	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Apr 20, 2016)	unknown	clinical testing	mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV002214957	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23028790, 30675864, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000486211

Counsyl

criteria provided, single submitter

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

Likely pathogenic
(Apr 20, 2016)

unknown

clinical testing

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

Citation Link,

SCV002214957

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 21, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.

Sturm M, Herebian D, Mueller M, Laryea MD, Spiekerkoetter U.

PLoS One. 2012;7(9):e45110. doi: 10.1371/journal.pone.0045110. Epub 2012 Sep 17.

PubMed [citation]

PMID:: 23028790
PMCID:: PMC3444485

[Medium-chain acyl-CoA dehydrogenase deficiency: neonatal screening and follow-uP].

Tong F, Jiang PP, Yang RL, Huang XL, Zhou XL, Hong F, Qian GL, Zhao ZY, Shu Q.

Zhongguo Dang Dai Er Ke Za Zhi. 2019 Jan;21(1):52-57. Chinese.

PubMed [citation]

PMID:: 30675864
PMCID:: PMC7390178

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000486211.3

#	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 Invitae, SCV002214957.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370802). Disruption of the initiator codon has been observed in individual(s) with medium-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 23028790, 30675864). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the ACADM mRNA. The next in-frame methionine is located at codon 87.

#	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 28, 2024

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