chr2-240873022-G-A
Variant summary
Our verdict is Pathogenic. Variant got 22 ACMG points: 22P and 0B. PS1PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000030.3(AGXT):c.568G>A(p.Gly190Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000308 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G190A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000030.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 22 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGXT | NM_000030.3 | c.568G>A | p.Gly190Arg | missense_variant | 5/11 | ENST00000307503.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGXT | ENST00000307503.4 | c.568G>A | p.Gly190Arg | missense_variant | 5/11 | 1 | NM_000030.3 | P1 | |
AGXT | ENST00000472436.1 | n.588G>A | non_coding_transcript_exon_variant | 5/5 | 2 | ||||
AGXT | ENST00000476698.1 | n.305G>A | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249624Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135046
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461662Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727156
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type I Pathogenic:6
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 28, 2024 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 05, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jun 30, 2021 | - - |
Likely pathogenic, criteria provided, single submitter | literature only | Counsyl | Nov 06, 2014 | - - |
Pathogenic, no assertion criteria provided | in vitro | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 02, 2022 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27935012, 27568336, 18282470, 15849466, 31589614, 24988064, 23810941, 30341509, 10541294, 25629080, 19571789, 17460142, 9604803) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 190 of the AGXT protein (p.Gly190Arg). This variant is present in population databases (rs180177239, gnomAD 0.01%). This missense change has been observed in individuals with primary hyperoxaluria (PMID: 9604803, 15849466, 15961946, 27568336, 27935012). It has also been observed to segregate with disease in related individuals. This variant is also known as c.690G>A. ClinVar contains an entry for this variant (Variation ID: 189047). 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. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at