NM_000030.3(AGXT):c.245G>A (p.Gly82Glu) AND Primary hyperoxaluria, type I

Germline classification:: Pathogenic/Likely pathogenic (7 submissions)
Last evaluated:: Dec 15, 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:: RCV000005997.24

Allele description [Variation Report for NM_000030.3(AGXT):c.245G>A (p.Gly82Glu)]

NM_000030.3(AGXT):c.245G>A (p.Gly82Glu)

Gene:

AGXT:alanine--glyoxylate aminotransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.3

Genomic location:

Preferred name:

NM_000030.3(AGXT):c.245G>A (p.Gly82Glu)

HGVS:

NC_000002.12:g.240869249G>A
NG_008005.1:g.5505G>A
NM_000030.3:c.245G>AMANE SELECT
NP_000021.1:p.Gly82Glu
NP_000021.1:p.Gly82Glu
NC_000002.11:g.241808666G>A
NM_000030.2:c.245G>A
P21549:p.Gly82Glu

Protein change:

G82E; GLY82GLU

Links:

UniProtKB: P21549#VAR_008878; OMIM: 604285.0004; dbSNP: rs121908522

NCBI 1000 Genomes Browser:

rs121908522

Molecular consequence:

NM_000030.3:c.245G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary hyperoxaluria, type I (HP1)
Synonyms:: OXALOSIS I; Primary hyperoxaluria type 1; Oxalosis 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009823; MedGen: C0268164; Orphanet: 416; Orphanet: 93598; OMIM: 259900

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Homo sapiens zinc finger protein 792 (ZNF792), mRNA
Homo sapiens zinc finger protein 792 (ZNF792), mRNA
gi|1519313968|ref|NM_175872.5|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026179	OMIM	no assertion criteria provided	Pathogenic (Nov 17, 2000)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 1349575, 10960483
SCV000172451	GeneReviews	no classification provided	not provided	germline	literature only
SCV000239620	Clinical Biochemistry Laboratory, Health Services Laboratory	no assertion criteria provided	Pathogenic (Nov 27, 2014)	germline	in vitro	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000485912	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Mar 7, 2016)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18282470, 1349575, 24988064, 10960483, 17696873 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV002106577	Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics	no assertion criteria provided	Pathogenic (Jan 17, 2019)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004047613	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004194572	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 15, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing, literature only, in vitro
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation-based diagnostic testing for primary hyperoxaluria type 1: survey of results.

Coulter-Mackie MB, Lian Q, Applegarth DA, Toone J, Waters PJ, Vallance H.

Clin Biochem. 2008 May;41(7-8):598-602. doi: 10.1016/j.clinbiochem.2008.01.018. Epub 2008 Feb 7.

PubMed [citation]

PMID:: 18282470

A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1.

Purdue PE, Lumb MJ, Allsop J, Minatogawa Y, Danpure CJ.

Genomics. 1992 May;13(1):215-8.

PubMed [citation]

PMID:: 1349575

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000026179.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Purdue et al. (1992) found a G-to-A transition at nucleotide 367 of the AGXT cDNA, which was predicted to cause a glycine-to-glutamate substitution at residue 82 (G82Q) of the AGT protein. The mutation was located in exon 2 and led to the loss of an AvaI restriction site. The patient was homozygous. The same mutation was found in homozygous state in 1 related and 2 unrelated patients with type I primary hyperoxaluria (259900). One other phenotypically similar patient lacked the mutation, however.

Lumb and Danpure (2000) noted that AGT carrying the G82E substitution does not affect the stability or mitochondria targeting of AGT, but eliminates its catalytic activity. Using recombinant proteins expressed in E. coli, they showed that AGT with this substitution did not bind the pyridoxal phosphate cofactor.

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

From GeneReviews, SCV000172451.3

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

#	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

From Clinical Biochemistry Laboratory, Health Services Laboratory, SCV000239620.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

#	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

From Counsyl, SCV000485912.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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

From Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics, SCV002106577.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (1)

#	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		1	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047613.2

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

Description

The observed missense variant c.245G>A (p.Gly82Glu) in gene has been reported in homozygous and compound heterozygous state individuals affected with Hyperoxaluria, primary (Milliner DS et al. 2022; Coulter-Mackie MB et al. 2001). Experimental studies have shown that this missense change affects AGXT function (Cellini B et al. 2007). The p.Gly82Glu variant has allele frequency 0.002% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic / Pathogenic (multiple submitters). The amino acid change p.Gly82Glu in AGXT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 82 is changed to a Glu changing protein sequence and it might alter its composition and physico-chemical properties. 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004194572.2

#	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 16, 2024

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