NM_000030.3:c.866G>A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000030.3(AGXT):c.866G>A(p.Arg289His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,549,970 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000030.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00130 AC: 198AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000980 AC: 150AN: 153122Hom.: 0 AF XY: 0.000952 AC XY: 77AN XY: 80906
GnomAD4 exome AF: 0.000416 AC: 582AN: 1397628Hom.: 1 Cov.: 31 AF XY: 0.000406 AC XY: 280AN XY: 689272
GnomAD4 genome AF: 0.00130 AC: 198AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.00125 AC XY: 93AN XY: 74492
ClinVar
Submissions by phenotype
Primary hyperoxaluria, type I Uncertain:3
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Found in cis with c.1076T>C (p.Leu359Pro) -
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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Uncertain:2Benign:1
BS1 -
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not specified Uncertain:1
Variant summary: AGXT c.866G>A (p.Arg289His) results in a non-conservative amino acid change located in the Aminotransferase class V domain (IPR000192) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00098 in 153122 control chromosomes, particularly at a frequency of 0.0036 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.5-fold of the estimated maximal expected allele frequency for a pathogenic variant in AGXT causing Primary Hyperoxaluria Type 1 phenotype (0.0024), suggesting that the variant may be a benign polymorphism. Nevertheless, c.866G>A has been reported in the literature in a homozygous individual affected with Primary Hyperoxaluria Type 1 (Murad_2021). It has also been reported as part of complex alleles in additional individuals affected with Primary Hyperoxaluria Type 1 (Williams_2009, Williams_2015). These reports do not provide unequivocal conclusions about association of the variant with Primary Hyperoxaluria Type 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign and three ClinVar submitters (evaluation after 2014) cite it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at