NM_000016.5(ACADM):c.233T>C (p.Ile78Thr) AND not provided

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 19, 2018
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:: RCV000077885.7

Allele description

NM_000016.5(ACADM):c.233T>C (p.Ile78Thr)

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.233T>C (p.Ile78Thr)

Other names:

p.I78T:ATT>ACT

HGVS:

NC_000001.11:g.75732869T>C
NG_007045.2:g.13512T>C
NM_000016.5:c.233T>C
NM_001127328.2:c.245T>C
NM_001286042.1:c.125T>C
NM_001286043.1:c.233T>C
NM_001286044.1:c.-153T>C
NP_000007.1:p.Ile78Thr
NP_000007.1:p.Ile78Thr
NP_000007.1:p.Ile78Thr
NP_001120800.1:p.Ile82Thr
NP_001272971.1:p.Ile42Thr
NP_001272972.1:p.Ile78Thr
LRG_838t1:c.233T>C
LRG_838:g.13512T>C
LRG_838p1:p.Ile78Thr
NC_000001.10:g.76198554T>C
NM_000016.4:c.233T>C
P11310:p.Ile78Thr

Protein change:

I42T

Links:

UniProtKB: P11310#VAR_015954; dbSNP: rs398123074

NCBI 1000 Genomes Browser:

rs398123074

Molecular consequence:

NM_001286044.1:c.-153T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000016.5:c.233T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127328.2:c.245T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286042.1:c.125T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286043.1:c.233T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000229989	EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Oct 18, 2013)	germline	clinical testing	Citation Link,
SCV000238590	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 19, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000229989

EGL Genetic Diagnostics, Eurofins Clinical Diagnostics

criteria provided, single submitter

(EGL Classification Definitions)

Pathogenic
(Oct 18, 2013)

germline

clinical testing

Citation Link,

SCV000238590

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 19, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000229989.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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		3	not provided	not provided	not provided

From GeneDx, SCV000238590.11

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

Description

The I78T missense variant in the ACADM gene has been reported previously in association with medium chain-acyl-CoA dehydrogenase (MCAD) deficiency (Andresen et al., 2001; Sturm et al. 2012; Derks et al. 2014). Expression studies found that I78T is associated with a considerable decrease in MCAD enzyme activity compared to the wild-type protein (Andresen et al., 2001). I78T was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, we interpret I78T to be a pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2021

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