rs34116584
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM5BP4_ModerateBP6BS2_Supporting
The NM_000030.3(AGXT):c.32C>A(p.Pro11His) variant causes a missense change. The variant allele was found at a frequency of 0.000582 in 1,612,894 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000030.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGXT | NM_000030.3 | c.32C>A | p.Pro11His | missense_variant | 1/11 | ENST00000307503.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGXT | ENST00000307503.4 | c.32C>A | p.Pro11His | missense_variant | 1/11 | 1 | NM_000030.3 | P1 | |
AGXT | ENST00000472436.1 | n.52C>A | non_coding_transcript_exon_variant | 1/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000480 AC: 73AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000381 AC: 94AN: 246678Hom.: 2 AF XY: 0.000388 AC XY: 52AN XY: 134068
GnomAD4 exome AF: 0.000592 AC: 865AN: 1460620Hom.: 3 Cov.: 34 AF XY: 0.000607 AC XY: 441AN XY: 726580
GnomAD4 genome AF: 0.000479 AC: 73AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74444
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type I Uncertain:2
Uncertain significance, no assertion criteria provided | in vitro | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
AGXT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 26, 2022 | The AGXT c.32C>A variant is predicted to result in the amino acid substitution p.Pro11His. To our knowledge, this variant has not been reported in the literature. However, a different amino acid substitution affecting the same residue (p.Pro11Arg) has been reported to impact the catalytic activity of the AGT enzyme (Williams et al. 2009. PubMed ID: 19479957). The c.32C>A (p.Pro11His) variant is reported in 0.14% of alleles in individuals of East Asian descent in gnomAD, including 2 homozygotes (http://gnomad.broadinstitute.org/variant/2-241808314-C-A). While we suspect this variant is benign, at this time we interpret its clinical significance as uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at