NM_000159.4(GCDH):c.1116del (p.Asn373fs) AND Glutaric aciduria, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 7, 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:: RCV001907613.4

Allele description [Variation Report for NM_000159.4(GCDH):c.1116del (p.Asn373fs)]

NM_000159.4(GCDH):c.1116del (p.Asn373fs)

Gene:

GCDH:glutaryl-CoA dehydrogenase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_000159.4(GCDH):c.1116del (p.Asn373fs)

HGVS:

NC_000019.10:g.12897736del
NG_009292.1:g.11577del
NG_033049.1:g.26538del
NM_000159.4:c.1116delMANE SELECT
NM_013976.5:c.1116del
NP_000150.1:p.Asn373fs
NP_039663.1:p.Asn373fs
NC_000019.9:g.13008549del
NC_000019.9:g.13008550del
NR_102316.1:n.1279del
NR_102317.1:n.1497del

Protein change:

N373fs

Links:

dbSNP: rs2145954876

NCBI 1000 Genomes Browser:

rs2145954876

Molecular consequence:

NM_000159.4:c.1116del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_013976.5:c.1116del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_102316.1:n.1279del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_102317.1:n.1497del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Glutaric aciduria, type 1
Synonyms:: GA I; Glutaryl-CoA dehydrogenase deficiency; Glutaric acidemia type I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009281; MedGen: C0268595; Orphanet: 25; OMIM: 231670

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002122482	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 7, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8900228, 10960496, 25762492, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002122482

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 7, 2021)

germline

clinical testing

PubMed (4)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Glutaric aciduria type I in the Arab and Jewish communities in Israel.

Anikster Y, Shaag A, Joseph A, Mandel H, Ben-Zeev B, Christensen E, Elpeleg ON.

Am J Hum Genet. 1996 Nov;59(5):1012-8.

PubMed [citation]

PMID:: 8900228
PMCID:: PMC1914820

Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.

Busquets C, Merinero B, Christensen E, Gelpí JL, Campistol J, Pineda M, Fernández-Alvarez E, Prats JM, Sans A, Arteaga R, Martí M, Campos J, Martínez-Pardo M, Martínez-Bermejo A, Ruiz-Falcó ML, Vaquerizo J, Orozco M, Ugarte M, Coll MJ, Ribes A.

Pediatr Res. 2000 Sep;48(3):315-22.

PubMed [citation]

PMID:: 10960496

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002122482.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GCDH protein in which other variant(s) (p.Asn392Metfs*9) have been determined to be pathogenic (PMID: 8900228, 10960496, 25762492). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with GCDH-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn373Ilefs*28) in the GCDH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acid(s) of the GCDH protein.

#	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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