NM_000030.3(AGXT):c.653C>T (p.Ser218Leu) AND Primary hyperoxaluria, type I

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Sep 24, 2014
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:: RCV000169358.17

Allele description [Variation Report for NM_000030.3(AGXT):c.653C>T (p.Ser218Leu)]

NM_000030.3(AGXT):c.653C>T (p.Ser218Leu)

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.653C>T (p.Ser218Leu)

HGVS:

NC_000002.12:g.240874035C>T
NG_008005.1:g.10291C>T
NM_000030.3:c.653C>TMANE SELECT
NP_000021.1:p.Ser218Leu
NP_000021.1:p.Ser218Leu
NC_000002.11:g.241813452C>T
NM_000030.2:c.653C>T
P21549:p.Ser218Leu

Protein change:

S218L

Links:

UniProtKB: P21549#VAR_060559; dbSNP: rs180177253

NCBI 1000 Genomes Browser:

rs180177253

Molecular consequence:

NM_000030.3:c.653C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000220729	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Sep 24, 2014)	unknown	literature only	PubMed (6) [See all records that cite these PMIDs] 20573805, 18282470, 12899834, 16971151, 22018727, 15963748 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV000239668	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,
SCV002076473	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 8, 2021)	germline	clinical testing
SCV004047420	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]

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, in vitro
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration.

Perera MT, Sharif K, Lloyd C, Foster K, Hulton SA, Mirza DF, McKiernan PJ.

Nephrol Dial Transplant. 2011 Jan;26(1):354-9. doi: 10.1093/ndt/gfq353. Epub 2010 Jun 23.

PubMed [citation]

PMID:: 20573805

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

See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000220729.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (6)

#	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 Clinical Biochemistry Laboratory, Health Services Laboratory, SCV000239668.1

#	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 Natera, Inc., SCV002076473.1

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

#	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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047420.1

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

Description

The AGXT c.653C>T (p.Ser218Leu) variant has been observed to be homozygous in individuals affected with primary hyperoxaluria type I (Coulter-Mackie MB et al., 2005). This variant has been reported to affect AGXT protein function (Oppici E et al., 2011). This variant has allele frequency of 0.001% in the gnomad and novel in 1000 genome database. This variant has been submitted to ClinVar as Pathogenic. The amino acid Ser at position 218 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ser218Leu in AGXT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. 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

Last Updated: Apr 20, 2024

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