NM_000016.5(ACADM):c.157C>T (p.Arg53Cys) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Aug 1, 2019
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:: RCV000176961.8

Allele description

NM_000016.5(ACADM):c.157C>T (p.Arg53Cys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p31.1

Genomic location:

Preferred name:

NM_000016.5(ACADM):c.157C>T (p.Arg53Cys)

HGVS:

NC_000001.11:g.75732682C>T
NG_007045.2:g.13325C>T
NM_000016.5:c.157C>T
NM_001127328.2:c.169C>T
NM_001286042.1:c.49C>T
NM_001286043.1:c.157C>T
NM_001286044.1:c.-229C>T
NP_000007.1:p.Arg53Cys
NP_000007.1:p.Arg53Cys
NP_000007.1:p.Arg53Cys
NP_001120800.1:p.Arg57Cys
NP_001272971.1:p.Arg17Cys
NP_001272972.1:p.Arg53Cys
LRG_838t1:c.157C>T
LRG_838:g.13325C>T
LRG_838p1:p.Arg53Cys
NC_000001.10:g.76198367C>T
NM_000016.4:c.157C>T
P11310:p.Arg53Cys

Protein change:

R17C

Links:

UniProtKB: P11310#VAR_000317; dbSNP: rs398123072

NCBI 1000 Genomes Browser:

rs398123072

Molecular consequence:

NM_001286044.1:c.-229C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000016.5:c.157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127328.2:c.169C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286042.1:c.49C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286043.1:c.157C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000268474	ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 20, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000487011	Counsyl	no assertion criteria provided	Likely pathogenic (Sep 23, 2016)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 15832312, 24623196, 8535441, 26947917, 20434380, 8102510, 19649258, 7730333
SCV000893467	Fulgent Genetics,Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000943514	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 1, 2019)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 22796001, 15832312, 24623196, 26947917, 8102510, 16737882, 20434380, 28492532

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	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

Comparison between medium-chain acyl-CoA dehydrogenase mutant proteins overexpressed in bacterial and mammalian cells.

Jensen TG, Bross P, Andresen BS, Lund TB, Kristensen TJ, Jensen UB, Winther V, Kølvraa S, Gregersen N, Bolund L.

Hum Mutat. 1995;6(3):226-31.

PubMed [citation]

PMID:: 8535441

A novel tandem mass spectrometry method for rapid confirmation of medium- and very long-chain acyl-CoA dehydrogenase deficiency in newborns.

ter Veld F, Mueller M, Kramer S, Haussmann U, Herebian D, Mayatepek E, Laryea MD, Primassin S, Spiekerkoetter U.

PLoS One. 2009 Jul 30;4(7):e6449. doi: 10.1371/journal.pone.0006449.

PubMed [citation]

PMID:: 19649258
PMCID:: PMC2715108

See all PubMed Citations (12)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000268474.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing (GTR000500814.1)	PubMed (1)

#	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	(GTR000500814.1)	2	not provided	not provided	not provided

From Counsyl, SCV000487011.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

#	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 Fulgent Genetics,Fulgent Genetics, SCV000893467.1

#	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 Invitae, SCV000943514.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces arginine with cysteine at codon 53 of the ACADM protein (p.Arg53Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs398123072, ExAC 0.002%). This variant has been observed in combination with another ACADM variant in individuals affected with MCAD deficiency (PMID: 8102510, 15832312, 16737882, 20434380, 22796001, 24623196). This variant is also known as R28C in the literature. ClinVar contains an entry for this variant (Variation ID: 92258). Experimental studies have shown that this missense change disrupts ACADM protein function (PMID: 8102510, 26947917). 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: May 1, 2021

ClinVar

Relating variation to medicine