Report


This variant from GLY to ARG occurring at position 269 of gene TNK2 (UniProd Id Q07912 and Ensembl transcript Id ENST00000333602) and mapped on the PDB, PDB Id 1u46_B, is predicted structurally Damaging by Missense3D [1] (structural features disrupted: Buried Gly replaced;  Buried H-bond breakage;  Cavity altered;  Buried / exposed switch).

This variant has the following phenotypic annotations: ClinVar: -, Humsavar: -

This variant identified by the dbSNP Id rs753548814, has a minor allele frequency (MAF) of 4.061e-06 according to the gnomAD database. It occurs in a chromosome region, which has a percentile conservation score (CCR) of 49. Regions above the 95th percentile are considered constrained and less likely to tolerate variations [2]. The gene in which this variant occurs has a PLi score [3] of 0.0 and RVIS score [4] of 1.13 (89.0%)


References:
	1. J Mol Biol 2019 May 17;431(11):2197-2212. doi: 10.1016/j.jmb.2019.04.009
	2. Nat Genet 2019 Jan;51(1):88-95. doi: 10.1038/s41588-018-0294-6
	3. Nucleic Acids Res 2017 Jan 4;45(D1):D840-D845. doi: 10.1093/nar/gkw971
	4. PLoS Genet 2013;9(8):e1003709. doi: 10.1371/journal.pgen.1003709.


Structural features explanation:
	Buried Gly replaced: The substitution replaces a buried glycine. 
	Buried H-bond breakage: The substitution breaks all side-chain / side-chain H-bond(s) and/or side-chain / main-chain H-bond(s) formed by the wild type which was buried. The maximum H-bond N-O length is 3.9 angstrom. 
	Cavity altered: The substitution leads to an expansion or contraction of the cavity volume of > 70 angstrom^3. Cavity also refers to a pocket on the surface.  
	Buried / exposed switch: The substitution results in a change between buried and exposed state of the target variant residue. (RSA < 9% for buried and the difference between RSA has to be at least 5%.)