Submissions for variant NM_001371395.1(USP53):c.1702G>T (p.Asp568Tyr)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002471943	SCV002767604	uncertain significance	Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	2020-07-02	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with with low-GGT intrahepatic cholestasis (PMID: 32124521). (I) 0106 - This gene is associated with autosomal recessive disease (PMID: 32124521). (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to tyrosine (exon 15). (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (273 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Labcorp Genetics (formerly Invitae), Labcorp	RCV002571471	SCV003281264	likely benign	not provided	2024-10-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002571472	SCV003556941	uncertain significance	Inborn genetic diseases	2021-07-06	criteria provided, single submitter	clinical testing	The c.1702G>T (p.D568Y) alteration is located in exon 15 (coding exon 12) of the USP53 gene. This alteration results from a G to T substitution at nucleotide position 1702, causing the aspartic acid (D) at amino acid position 568 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics	RCV002471943	SCV003835397	uncertain significance	Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	2022-09-23	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV002471943	SCV005438497	uncertain significance	Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss	2024-12-18	criteria provided, single submitter	clinical testing