NM_000030.3(AGXT):c.33dup (p.Lys12fs) AND Alanine glyoxylate aminotransferase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 11, 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:: RCV003993816.1

Allele description [Variation Report for NM_000030.3(AGXT):c.33dup (p.Lys12fs)]

NM_000030.3(AGXT):c.33dup (p.Lys12fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2q37.3

Genomic location:

Preferred name:

NM_000030.3(AGXT):c.33dup (p.Lys12fs)

Other names:

33_34insC; NP_000021.1:p.Lys12fs; NM_000030.2:c.33_34insC

HGVS:

NC_000002.12:g.240868898dup
NG_008005.1:g.5154dup
NM_000030.3:c.33dupMANE SELECT
NP_000021.1:p.Lys12fs
NC_000002.11:g.241808307_241808308insC
NC_000002.11:g.241808315dup
NM_000030.2:c.33dup
NM_000030.2:c.33dupC
NM_000030.3:c.33dupCMANE SELECT
NP_000021.1:p.Lys12GlnfsTer156

Protein change:

K12fs

Links:

OMIM: 604285.0015; dbSNP: rs180177201

NCBI 1000 Genomes Browser:

rs180177201

Molecular consequence:

NM_000030.3:c.33dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Alanine glyoxylate aminotransferase deficiency
Identifiers:: MONDO: MONDO:0100278; MedGen: CN305373

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004812553	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15110324, 20301460, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004812553

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 11, 2023)

germline

clinical testing

PubMed (3)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The major allele of the alanine:glyoxylate aminotransferase gene: seven novel mutations causing primary hyperoxaluria type 1.

Coulter-Mackie MB, Applegarth D, Toone JR, Henderson H.

Mol Genet Metab. 2004 May;82(1):64-8.

PubMed [citation]

PMID:: 15110324

Primary Hyperoxaluria Type 1.

Milliner DS, Harris PC, Sas DJ, Cogal AG, Lieske JC.

2002 Jun 19 [updated 2022 Feb 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301460

See all PubMed Citations (3)

Details of each submission

From Molecular Genetics, Royal Melbourne Hospital, SCV004812553.1

#	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 in AGXT is a frameshift variant predicted to cause a premature stop codon, p.(Lys12Glnfs*156), in biologically relevant exon 4/11 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. The highest population minor allele frequency in the population database gnomAD v3.1 is 0.02% (1/4,750 alleles) in the South Asian population, which is consistent with recessive disease. The variant is one of the most commonly reported pathogenic variants in AGXT. It has been identified in the homozygous state and compound heterozygous with a second pathogenic variant in multiple individuals with clinical/biochemical diagnosis of primary hyperoxaluria (PMID: 15110324, 20301460). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM3_Strong, PM2_Supporting.

#	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

Last Updated: May 26, 2024

ClinVar

Relating variation to medicine