2-240875185-T-C
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000030.3(AGXT):c.757T>C(p.Cys253Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,224 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 (★★). Synonymous variant affecting the same amino acid position (i.e. C253C) has been classified as Likely benign.
Frequency
Consequence
NM_000030.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGXT | NM_000030.3 | c.757T>C | p.Cys253Arg | missense_variant | 7/11 | ENST00000307503.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGXT | ENST00000307503.4 | c.757T>C | p.Cys253Arg | missense_variant | 7/11 | 1 | NM_000030.3 | P1 | |
AGXT | ENST00000476698.1 | n.409T>C | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251370Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135888
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461224Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726964
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type I Pathogenic:2
Pathogenic, no assertion criteria provided | in vitro | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 29, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 02, 2022 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects AGXT function (PMID: 17495019, 22923379, 24718375). 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. ClinVar contains an entry for this variant (Variation ID: 204126). This missense change has been observed in individual(s) with Primary Hyperoxaluria Type 1 (PMID: 15849466, 17495019). This variant is present in population databases (rs180177264, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 253 of the AGXT protein (p.Cys253Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at