Submissions for variant NM_000546.6(TP53):c.459C>T (p.Pro153=)

gnomAD frequency: 0.00003  dbSNP: rs72661116

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000220191	SCV000274241	likely benign	Hereditary cancer-predisposing syndrome	2015-02-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000474641	SCV000557363	likely benign	Li-Fraumeni syndrome	2024-12-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000220191	SCV000686739	likely benign	Hereditary cancer-predisposing syndrome	2017-03-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000606755	SCV000730224	benign	not specified	2017-05-12	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo	RCV001270282	SCV001450502	likely benign	Colorectal cancer		criteria provided, single submitter	case-control
Sema4, Sema4	RCV000220191	SCV002530458	likely benign	Hereditary cancer-predisposing syndrome	2021-12-17	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV000220191	SCV002582591	likely benign	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002288857	SCV002582893	likely benign	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477723	SCV004221357	benign	not provided	2022-10-31	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000474641	SCV004823803	likely benign	Li-Fraumeni syndrome	2024-03-28	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357405	SCV001552872	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The TP53 p.Pro153= variant was identified in the literature in a patient with invasive ductal carcinoma of the breast (Al-Qasem 2011). The variant was also identified in dbSNP (ID: rs72661116) as "With Likely benign allele", ClinVar (classified as benign by GeneDx; and as likely benign by Ambry Genetics, Invitae and Color). The variant was not identified in LOVD 3.0 or UMD-LSDB. The variant was identified in control databases in 29 of 277036 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 18 of 30782 chromosomes (freq: 0.0006), African in 1 of 24026 chromosomes (freq: 0.00004), Other in 2 of 6460 chromosomes (freq: 0.0003), Latino in 1 of 34414 chromosomes (freq: 0.00003), European in 5 of 126558 chromosomes (freq: 0.00004), East Asian in 1 of 18868 chromosomes (freq: 0.00005), and Finnish in 1 of 25780 chromosomes (freq: 0.00004); it was not observed in the Ashkenazi Jewish population. The p.Pro153= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.