NM_000016.6(ACADM):c.1125A>G (p.Ile375Met) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 31, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000795831.9

Allele description [Variation Report for NM_000016.6(ACADM):c.1125A>G (p.Ile375Met)]

NM_000016.6(ACADM):c.1125A>G (p.Ile375Met)

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.1125A>G (p.Ile375Met)

HGVS:

NC_000001.11:g.75761301A>G
NG_007045.2:g.41944A>G
NM_000016.6:c.1125A>GMANE SELECT
NM_001127328.3:c.1137A>G
NM_001286042.2:c.1017A>G
NM_001286043.2:c.1224A>G
NM_001286044.2:c.558A>G
NP_000007.1:p.Ile375Met
NP_000007.1:p.Ile375Met
NP_001120800.1:p.Ile379Met
NP_001272971.1:p.Ile339Met
NP_001272972.1:p.Ile408Met
NP_001272973.1:p.Ile186Met
LRG_838t1:c.1125A>G
LRG_838:g.41944A>G
LRG_838p1:p.Ile375Met
NC_000001.10:g.76226986A>G
NM_000016.4:c.1125A>G
NM_000016.5:c.1125A>G

Protein change:

I186M

Links:

dbSNP: rs201809827

NCBI 1000 Genomes Browser:

rs201809827

Molecular consequence:

NM_000016.6:c.1125A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127328.3:c.1137A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286042.2:c.1017A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286043.2:c.1224A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286044.2:c.558A>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000935309	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001461478	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 16, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000935309

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2021)

germline

clinical testing

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

SCV001461478

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 16, 2020)

germline

clinical testing

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

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000935309.5

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

Description

This sequence change replaces isoleucine with methionine at codon 375 of the ACADM protein (p.Ile375Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs201809827, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with ACADM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Natera, Inc., SCV001461478.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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