2-240868893-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000030.3(AGXT):āc.28C>Gā(p.Pro10Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,612,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000030.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246584Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134064
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460642Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 726592
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:1
The P10A variant in the AGXT gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P10A variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P10A variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, missense variants in nearby residues (T9N and P11R) have been reported in the Human Gene Mutation Database in association with PH1 (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret P10A as a variant of uncertain significance. -
Primary hyperoxaluria, type I Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at