Submissions for variant NM_177924.5(ASAH1):c.505T>C (p.Trp169Arg)

dbSNP: rs756455049

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV001728167	SCV004175760	pathogenic	Farber lipogranulomatosis	2023-03-01	criteria provided, single submitter	clinical testing	The missense/ splice region variant c.505T>C (p.Trp169Arg) in the ASAH1 gene has been reported previously in compound heterozygous and homozygous states in individuals affected with Farber's Disease. Experimental studies have shown that this missense change affects protein function (Gebai et al., 2018; Moghadam et al., 2019). This variant is reported with the allele frequency (0.0003%) in the gnomAD and novel in the 1000 genome database. It is submitted to ClinVar with varying interpretations as Pathogenic/ Likely Pathogenic. The amino acid Tryptophan at position 169 is changed to an Arginine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted as damaging by SIFT. The amino acid change p.Trp169Arg in ASAH1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001728167	SCV004805067	likely pathogenic	Farber lipogranulomatosis	2024-03-17	criteria provided, single submitter	research
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000171533	SCV000221732	likely pathogenic	not provided		flagged submission	research
OMIM	RCV001728167	SCV001976493	pathogenic	Farber lipogranulomatosis	2021-10-04	no assertion criteria provided	literature only