Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate
The NM_015570(AUTS2):c.118G>A(p.Ala40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 151794 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Verdict is Likely_benign. Variant got -1 ACMG points.
GnomAD3 genomes AF: 0.0000264AC: 4AN: 151794Hom.: 0Cov.: 32 GnomAD3 exomes AF: 0.0000217AC: 2AN: 92074Hom.: 0 AF XY: 0.00AC XY: 0AN XY: 52120 GnomAD4 exome AF: 0.0000128AC: 17AN: 1326420Hom.: 0 AF XY: 0.0000138AC XY: 9AN XY: 653552
Submissions by phenotype
|Uncertain significance, criteria provided, single submitter||clinical testing||GeneDx||May 02, 2016||The A40T variant in the AUTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 4400 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 A40T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved mammals. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret A40T as a variant of uncertain significance. -|
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