2-240873038-T-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000030.3(AGXT):āc.584T>Gā(p.Met195Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,528 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M195L) has been classified as Pathogenic.
Frequency
Consequence
NM_000030.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGXT | NM_000030.3 | c.584T>G | p.Met195Arg | missense_variant | 5/11 | ENST00000307503.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGXT | ENST00000307503.4 | c.584T>G | p.Met195Arg | missense_variant | 5/11 | 1 | NM_000030.3 | P1 | |
AGXT | ENST00000472436.1 | n.604T>G | non_coding_transcript_exon_variant | 5/5 | 2 | ||||
AGXT | ENST00000476698.1 | n.321T>G | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461528Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727118
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type I Pathogenic:4
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 05, 2022 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 15, 2021 | - - |
Pathogenic, no assertion criteria provided | in vitro | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 15, 2022 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 195 of the AGXT protein (p.Met195Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with primary hyperoxaluria, type 1 (PMID: 15961946, 24988064; Invitae). ClinVar contains an entry for this variant (Variation ID: 204113). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects AGXT function (PMID: 24718375). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at