The missense variant p.G350D in AGXT (NM_000030.3) has been reported previously in multiple affected indviduals (Du DF et al; Rao NM et al). The variant was submitted to ClinVar as Likely Pathogenic. The p.G350D variant is observed in 11/30,610 (0.0359%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between glycine and aspartic acid. The p.G350D missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 350 of AGXT is conserved in all mammalian species. The nucleotide c.1049 in AGXT is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000030.3(AGXT):c.1049G>A (p.Gly350Asp)
Germline
Classification
Help
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.
(8)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000030.3(AGXT):c.1049G>A (p.Gly350Asp)
Variation ID: 188986 Accession: VCV000188986.19
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q37.3 2: 240878128 (GRCh38) [ NCBI UCSC ] 2: 241817545 (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 29, 2015 Oct 13, 2024 Jan 3, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000030.3:c.1049G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000021.1:p.Gly350Asp missense NC_000002.12:g.240878128G>A NC_000002.11:g.241817545G>A NG_008005.1:g.14384G>A P21549:p.Gly350Asp - Protein change
- G350D
- Other names
- -
- Canonical SPDI
- NC_000002.12:240878127:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 | - | - |
GRCh38 GRCh37 |
914 | 1034 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jan 3, 2024 | RCV000169365.20 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 10, 2023 | RCV001067841.16 | |
| Pathogenic (1) |
no assertion criteria provided
|
Oct 24, 2018 | RCV001328117.9 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jan 03, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Primary hyperoxaluria, type I
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004192231.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Likely pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Primary hyperoxaluria, type I
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002073273.1
First in ClinVar: Feb 05, 2022 Last updated: Feb 05, 2022 |
Comment:
The missense variant p.G350D in AGXT (NM_000030.3) has been reported previously in multiple affected indviduals (Du DF et al; Rao NM et al). The variant … (more)
The missense variant p.G350D in AGXT (NM_000030.3) has been reported previously in multiple affected indviduals (Du DF et al; Rao NM et al). The variant was submitted to ClinVar as Likely Pathogenic. The p.G350D variant is observed in 11/30,610 (0.0359%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between glycine and aspartic acid. The p.G350D missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 350 of AGXT is conserved in all mammalian species. The nucleotide c.1049 in AGXT is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. (less)
Clinical Features:
Nephrocalcinosis (present) , Nephrolithiasis (present)
|
|
|
Likely pathogenic
(Sep 25, 2014)
|
criteria provided, single submitter
Method: literature only
|
Primary hyperoxaluria, type I
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220737.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
|
Likely pathogenic
(Oct 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Primary hyperoxaluria, type I
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002809820.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Oct 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001232922.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 350 of the AGXT protein … (more)
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 350 of the AGXT protein (p.Gly350Asp). This variant is present in population databases (rs180177156, gnomAD 0.03%). This missense change has been observed in individual(s) with hyperoxaluria (PMID: 9604803, 23551880, 30341509, 35149915). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as G1171A. ClinVar contains an entry for this variant (Variation ID: 188986). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AGXT protein function. Experimental studies have shown that this missense change affects AGXT function (PMID: 22018727, 22923379, 30341509). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Nov 27, 2014)
|
no assertion criteria provided
Method: in vitro
|
Primary hyperoxaluria, type I
Affected status: yes
Allele origin:
germline
|
Clinical Biochemistry Laboratory, Health Services Laboratory
Accession: SCV000239699.1
First in ClinVar: Jul 21, 2015 Last updated: Jul 21, 2015 |
Result:
In vitro activity: 2.9% on majorallele; 7.6% on minor.
|
|
|
Pathogenic
(Oct 24, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Primary hyperoxaluria
Affected status: yes
Allele origin:
unknown
|
Sydney Genome Diagnostics, Children's Hospital Westmead
Accession: SCV001449178.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This patient is homozygous for a known pathogenic variant, c.1049G>A p.(Gly350Asp), in the AGXT gene. This variant (dbSNP: rs180177156) has been previously reported in the … (more)
This patient is homozygous for a known pathogenic variant, c.1049G>A p.(Gly350Asp), in the AGXT gene. This variant (dbSNP: rs180177156) has been previously reported in the homozygote form in a patient with primary hyperoxaluria type I (Rao et al 2014 J Neuroimaging 24:411-3). (less)
Number of individuals with the variant: 1
|
|
|
Likely pathogenic
(Aug 26, 2024)
|
no assertion criteria provided
Method: clinical testing
|
Primary hyperoxaluria, type I
Affected status: yes
Allele origin:
paternal
|
Chinese Inherited Urolithiasis Consortium, The Affiliated Yantai Yuhuangding Hospital of Qingdao University
Accession: SCV005368586.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Comment:
Variant_type:missense/MutationTaster:Disease_causing_automatic/CADD:Damaging/phyloP:Conserved/phastCons:Conserved/gnomAD_exome_EastAsian:0/ExAC_EastAsian:0/dbSNP:rs180177156
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Asian
Geographic origin: China
|
Comment:
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 350 of the AGXT protein (p.Gly350Asp). This variant is present in population databases (rs180177156, gnomAD 0.03%). This missense change has been observed in individual(s) with hyperoxaluria (PMID: 9604803, 23551880, 30341509, 35149915). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as G1171A. ClinVar contains an entry for this variant (Variation ID: 188986). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AGXT protein function. Experimental studies have shown that this missense change affects AGXT function (PMID: 22018727, 22923379, 30341509). For these reasons, this variant has been classified as Pathogenic.
Comment:
This patient is homozygous for a known pathogenic variant, c.1049G>A p.(Gly350Asp), in the AGXT gene. This variant (dbSNP: rs180177156) has been previously reported in the homozygote form in a patient with primary hyperoxaluria type I (Rao et al 2014 J Neuroimaging 24:411-3).
Comment:
Variant_type:missense/MutationTaster:Disease_causing_automatic/CADD:Damaging/phyloP:Conserved/phastCons:Conserved/gnomAD_exome_EastAsian:0/ExAC_EastAsian:0/dbSNP:rs180177156
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:
The missense variant p.G350D in AGXT (NM_000030.3) has been reported previously in multiple affected indviduals (Du DF et al; Rao NM et al). The variant was submitted to ClinVar as Likely Pathogenic. The p.G350D variant is observed in 11/30,610 (0.0359%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between glycine and aspartic acid. The p.G350D missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 350 of AGXT is conserved in all mammalian species. The nucleotide c.1049 in AGXT is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 350 of the AGXT protein (p.Gly350Asp). This variant is present in population databases (rs180177156, gnomAD 0.03%). This missense change has been observed in individual(s) with hyperoxaluria (PMID: 9604803, 23551880, 30341509, 35149915). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as G1171A. ClinVar contains an entry for this variant (Variation ID: 188986). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AGXT protein function. Experimental studies have shown that this missense change affects AGXT function (PMID: 22018727, 22923379, 30341509). For these reasons, this variant has been classified as Pathogenic.
Comment:
This patient is homozygous for a known pathogenic variant, c.1049G>A p.(Gly350Asp), in the AGXT gene. This variant (dbSNP: rs180177156) has been previously reported in the homozygote form in a patient with primary hyperoxaluria type I (Rao et al 2014 J Neuroimaging 24:411-3).
Comment:
Variant_type:missense/MutationTaster:Disease_causing_automatic/CADD:Damaging/phyloP:Conserved/phastCons:Conserved/gnomAD_exome_EastAsian:0/ExAC_EastAsian:0/dbSNP:rs180177156
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A comparison of the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses. | Zhao Y | World journal of urology | 2022 | PMID: 35149915 |
| Updated Genetic Testing of Primary Hyperoxaluria Type 1 in a Chinese Population: Results from a Single Center Study and a Systematic Review. | Du DF | Current medical science | 2018 | PMID: 30341509 |
| Stroke in primary hyperoxaluria type I. | Rao NM | Journal of neuroimaging : official journal of the American Society of Neuroimaging | 2014 | PMID: 23551880 |
| Rapid profiling of disease alleles using a tunable reporter of protein misfolding. | Pittman AM | Genetics | 2012 | PMID: 22923379 |
| Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with primary hyperoxaluria type I. | Oppici E | Molecular genetics and metabolism | 2012 | PMID: 22018727 |
| Mutation-based diagnostic testing for primary hyperoxaluria type 1: survey of results. | Coulter-Mackie MB | Clinical biochemistry | 2008 | PMID: 18282470 |
| Preliminary evidence for ethnic differences in primary hyperoxaluria type 1 genotype. | Coulter-Mackie MB | American journal of nephrology | 2005 | PMID: 15961945 |
| Identification of new mutations in primary hyperoxaluria type 1 (PH1). | von Schnakenburg C | Journal of nephrology | 1998 | PMID: 9604803 |
| http://www.uclh.nhs.uk/OurServices/ServiceA-Z/PATH/PATHBIOMED/CBIO/Documents/AGXT%20mutation%20database.pdf | - | - | - | - |
Text-mined citations for rs180177156 ...
HelpThese 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 Nov 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.