VCV000039486.37 - ClinVar

NM_000030.3(AGXT):c.1020A>G (p.Ile340Met)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

9 out of 13 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000030.3(AGXT):c.1020A>G (p.Ile340Met)

Variation ID: 39486 Accession: VCV000039486.37

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q37.3 2: 240878099 (GRCh38) [ NCBI UCSC ] 2: 241817516 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 24, 2015	Apr 13, 2025	Feb 3, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000030.3:c.1020A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000021.1:p.Ile340Met	missense
NC_000002.12:g.240878099A>G
NC_000002.11:g.241817516A>G
NG_008005.1:g.14355A>G
	P21549:p.Ile340Met

... more HGVS ... less HGVS

Protein change

I340M

Other names

Canonical SPDI

NC_000002.12:240878098:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.11122 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.10899

1000 Genomes Project 0.11122

The Genome Aggregation Database (gnomAD) 0.15200

Exome Aggregation Consortium (ExAC) 0.16526

The Genome Aggregation Database (gnomAD), exomes 0.19344

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.15916

The Genome Aggregation Database (gnomAD), exomes 0.16397

Trans-Omics for Precision Medicine (TOPMed) 0.14257

The Genome Aggregation Database (gnomAD) 0.15412

Links

ClinGen: CA343786 UniProtKB: P21549#VAR_000593 OMIM: 604285.0014 dbSNP: rs4426527 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
AGXT		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	971	1093

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Primary hyperoxaluria, type I	Benign/Likely benign (8)	criteria provided, multiple submitters, no conflicts	Nov 17, 2021	RCV000032682.31
not specified	Benign (2)	criteria provided, multiple submitters, no conflicts	Jun 26, 2016	RCV000247828.18
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 3, 2025	RCV001519689.18

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000301564.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016

Benign (Jun 26, 2016) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000343450.5 First in ClinVar: Dec 06, 2016 Last updated: Apr 13, 2025	Publications: PubMed (1) PubMed: 15802217 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AGXT Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed

Likely benign (May 28, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Primary hyperoxaluria, type I Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001136276.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020

Benign (Mar 06, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Primary hyperoxaluria, type I Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000429374.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)

Benign (Aug 07, 2018) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001856932.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: This variant is associated with the following publications: (PMID: 1703535, 33457257, 24205397, 30341509, 28906061, 15802217)

Likely benign (Nov 17, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Primary hyperoxaluria, type I Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002808379.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022

Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005261970.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024

Benign (Feb 03, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001728600.5 First in ClinVar: Jun 15, 2021 Last updated: Feb 25, 2025

Benign (Jul 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Primary hyperoxaluria, type I Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001761749.2 First in ClinVar: Jul 31, 2021 Last updated: Apr 13, 2025	Sex: mixed

Uncertain significance (Nov 27, 2014) N Not contributing to aggregate classification	no assertion criteria provided Method: in vitro	Primary hyperoxaluria, type I Affected status: yes Allele origin: germline	Clinical Biochemistry Laboratory, Health Services Laboratory Accession: SCV000239589.1 First in ClinVar: Jul 23, 2015 Last updated: Jul 23, 2015	Publications: PubMed (2) PubMed: 1349575‚ 10960483 Other databases http://www.uclh.nhs.uk/OurServic… http://www.uclh.nhs.uk/OurServices/ServiceA-Z/PATH/PATHBIOMED/CBIO/Documents/AGXT%20mutation%20database.pdf Result: In vitro activity: 76-117%

Benign (Oct 30, 2019) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	Primary hyperoxaluria type I Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002076484.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022

Benign (Sep 01, 2004) N Not contributing to aggregate classification	no assertion criteria provided Method: literature only	RECLASSIFIED - AGXT POLYMORPHISM Affected status: not provided Allele origin: germline	OMIM Accession: SCV000056445.4 First in ClinVar: Apr 04, 2013 Last updated: Apr 07, 2025	Publications: PubMed (2) PubMed: 15464418‚ 10960483 Comment on evidence: This variant, formerly titled HYPEROXALURIA, PRIMARY, TYPE I, has been reclassified as a polymorphism. Coulter-Mackie and Rumsby (2004) noted that the ile340-to-met (I340M) substitution results … (more) This variant, formerly titled HYPEROXALURIA, PRIMARY, TYPE I, has been reclassified as a polymorphism. Coulter-Mackie and Rumsby (2004) noted that the ile340-to-met (I340M) substitution results from a 1020A-G transition exon 10 of AGXT. Lumb and Danpure (2000) found that recombinant AGT carrying the P11L (604285.0002) and I340M variants (AGT(L11,M340)) associated with the minor allele had only 46 to 50% of the wildtype alanine:glyoxylate aminotransferase activity. The lower specific activity of the AGT(L11,M340) appeared to be entirely due to the presence of the P11L polymorphism rather than the I340M polymorphism, since the activity of AGT(L11) was about 25% of wildtype, and the activity of AGT(M340) was comparable to or higher than wildtype. (less)

not provided (-) N Not contributing to aggregate classification	no classification provided Method: literature only	Primary hyperoxaluria, type I Affected status: yes Allele origin: germline	GeneReviews Accession: SCV000172448.3 First in ClinVar: Jul 24, 2014 Last updated: Oct 01, 2022 Comment: One of the variants that defines the haplotype "minor AGXT allele"	Publications: BookShelf: NBK1283 BookShelf: NBK1283

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Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Primary Hyperoxaluria Type 1.	Adam MP	-	2024	PMID: 20301460
Overexpression of human alanine:glyoxylate aminotransferase in Escherichia coli: renaturation from guanidine-HCl and affinity for pyridoxal phosphate co-factor.	Coulter-Mackie MB	Protein expression and purification	2005	PMID: 15802217
Genetic heterogeneity in primary hyperoxaluria type 1: impact on diagnosis.	Coulter-Mackie MB	Molecular genetics and metabolism	2004	PMID: 15464418
Functional synergism between the most common polymorphism in human alanine:glyoxylate aminotransferase and four of the most common disease-causing mutations.	Lumb MJ	The Journal of biological chemistry	2000	PMID: 10960483
A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1.	Purdue PE	Genomics	1992	PMID: 1349575
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AGXT	-	-	-	-
http://www.uclh.nhs.uk/OurServices/ServiceA-Z/PATH/PATHBIOMED/CBIO/Documents/AGXT%20mutation%20database.pdf	-	-	-	-

Text-mined citations for rs4426527 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2025

ClinVar Genomic variation as it relates to human health

NM_000030.3(AGXT):c.1020A>G (p.Ile340Met)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs4426527 ...