NM_000027.4(AGA):c.3G>A (p.Met1Ile) AND Aspartylglucosaminuria

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 4, 2023
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:: RCV003236531.1

Allele description [Variation Report for NM_000027.4(AGA):c.3G>A (p.Met1Ile)]

NM_000027.4(AGA):c.3G>A (p.Met1Ile)

Gene:

AGA:aspartylglucosaminidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q34.3

Genomic location:

Preferred name:

NM_000027.4(AGA):c.3G>A (p.Met1Ile)

HGVS:

NC_000004.12:g.177442373C>T
NG_011845.2:g.5131G>A
NG_103920.1:g.85C>T
NM_000027.4:c.3G>AMANE SELECT
NM_001171988.2:c.3G>A
NP_000018.2:p.Met1Ile
NP_001165459.1:p.Met1Ile
NC_000004.11:g.178363527C>T
NM_000027.3:c.3G>A
NR_033655.2:n.65G>A

Protein change:

M1I

Molecular consequence:

NM_000027.4:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001171988.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000027.4:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171988.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033655.2:n.65G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Aspartylglucosaminuria (AGU)
Synonyms:: GLYCOASPARAGINASE; Aspartylglycosaminuria; Aspartylglucos-aminuria; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008830; MedGen: C0268225; Orphanet: 93; OMIM: 208400; Human Phenotype Ontology: HP:0012068

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003933749	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (May 4, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003933749

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(May 4, 2023)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003933749.2

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

Description

Variant summary: AGA c.3G>A (p.Met1?, aka p.Met1Ile) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. The first potential downstream in-frame start codon (ATG) is located at Met63, which is not a known initiation codon in any alternative transcripts. Truncations and pathogenic missense variants have been reported upstream of Met63 in affected individuals (HGMD), and been classified as pathogenic by our laboratory. The variant was absent in 251060 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3G>A in individuals affected with Aspartylglucosaminuria and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: Sep 3, 2023

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