2-236194987-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_212556.4(ASB18):c.1286G>A(p.Arg429His) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,613,736 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 Uncertain significance (★).
Frequency
Consequence
NM_212556.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248906Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135034
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461554Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727034
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
The R429H variant in the ASB18 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R429H variant was not observed at any significant frequency in approximately 6400 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 R429H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R429H as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at