chr2-240878086-T-A
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_000030.3(AGXT):c.1007T>A(p.Val336Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,056 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 (★★).
Frequency
Consequence
NM_000030.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250634Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135604
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461056Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726834
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type I Pathogenic:3
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not provided Pathogenic:1
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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AGXT protein function. ClinVar contains an entry for this variant (Variation ID: 204143). This missense change has been observed in individuals with primary hyperoxaluria type 1 (PMID: 25629080, 34082749). This variant is present in population databases (rs180177155, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 336 of the AGXT protein (p.Val336Asp). Experimental studies have shown that this missense change affects AGXT function (PMID: 18448374, 22529745). 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