Submissions for variant NM_017736.5(THUMPD1):c.491C>G (p.Pro164Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV004771662	SCV005382319	uncertain significance	Neurodevelopmental disorder with speech delay and variable ocular anomalies	2023-05-20	criteria provided, single submitter	clinical testing	The observed missense c.491C>G(p.Pro164Arg) variant in THUMPD1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Pro164Arg variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidences (Polyphen - Probably damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Pro at position 164 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. Another missense variant [c.490C>T (p.Pro164Ser)] on the same residue of this gene has previously been reported to be disease causing (Broly M, et al., 2022), suggesting that this residue might be of clinical significance. However, additional functional studies will be required to prove the pathogenicity of p.Pro164Arg variant. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).