NM_000126.4(ETFA):c.625del (p.Arg209fs) AND Multiple acyl-CoA dehydrogenase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 30, 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:: RCV001058139.7

Allele description [Variation Report for NM_000126.4(ETFA):c.625del (p.Arg209fs)]

NM_000126.4(ETFA):c.625del (p.Arg209fs)

Gene:

ETFA:electron transfer flavoprotein subunit alpha [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q24.2

Genomic location:

Preferred name:

NM_000126.4(ETFA):c.625del (p.Arg209fs)

HGVS:

NC_000015.10:g.76285676del
NG_007077.2:g.30794del
NM_000126.4:c.625delMANE SELECT
NM_001127716.2:c.478del
NP_000117.1:p.Arg209fs
NP_001121188.1:p.Arg160fs
NC_000015.9:g.76578017del
NM_000126.3:c.625del

Protein change:

R160fs

Links:

dbSNP: rs1209473816

NCBI 1000 Genomes Browser:

rs1209473816

Molecular consequence:

NM_000126.4:c.625del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127716.2:c.478del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Multiple acyl-CoA dehydrogenase deficiency (MADD)
Synonyms:: GA II; Ethylmalonic-adipicaciduria; Glutaric aciduria, type 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009282; MedGen: C0268596; Orphanet: 26791; OMIM: 231680

Recent activity

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Arabidopsis thaliana SET domain-containing protein (AT1G43245), mRNA
Arabidopsis thaliana SET domain-containing protein (AT1G43245), mRNA
gi|1063688389|ref|NM_148531.3|

Nucleotide
Mus musculus cilia and flagella associated protein 119 (Cfap119), transcript var...
Mus musculus cilia and flagella associated protein 119 (Cfap119), transcript variant 1, mRNA
gi|2219517893|ref|NM_001033040.4|

Nucleotide
Mus musculus cholinergic receptor, muscarinic 5, mRNA (cDNA clone MGC:155852 IMA...
Mus musculus cholinergic receptor, muscarinic 5, mRNA (cDNA clone MGC:155852 IMAGE:40129538), complete cds
gi|111308244|gb|BC120615.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001222686	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16510302, 23785301, 28492532
SCV004194711	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 26, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001222686

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 30, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004194711

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 26, 2023)

unknown

clinical testing

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

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

Electron transfer flavoprotein deficiency: functional and molecular aspects.

Schiff M, Froissart R, Olsen RK, Acquaviva C, Vianey-Saban C.

Mol Genet Metab. 2006 Jun;88(2):153-8. Epub 2006 Feb 28.

PubMed [citation]

PMID:: 16510302

Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency.

Kim SH, Scott SA, Bennett MJ, Carson RP, Fessel J, Brown HA, Ess KC.

PLoS Genet. 2013 Jun;9(6):e1003563. doi: 10.1371/journal.pgen.1003563. Epub 2013 Jun 13.

PubMed [citation]

PMID:: 23785301
PMCID:: PMC3681725

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001222686.5

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

Description

This sequence change creates a premature translational stop signal (p.Arg209Aspfs*4) in the ETFA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ETFA are known to be pathogenic (PMID: 16510302, 23785301). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ETFA-related conditions. ClinVar contains an entry for this variant (Variation ID: 853348). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

From Baylor Genetics, SCV004194711.1

#	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

Last Updated: Sep 29, 2024

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