Submissions for variant NM_000546.6(TP53):c.102C>G (p.Pro34=)

gnomAD frequency: 0.00004  dbSNP: rs11575998

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165856	SCV000216605	likely benign	Hereditary cancer-predisposing syndrome	2014-09-03	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.
GeneDx	RCV000760099	SCV000514933	likely benign	not provided	2019-03-15	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21722702, 19165225, 18798306, 25847421, 25935255)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081857	SCV000629766	likely benign	Li-Fraumeni syndrome	2025-01-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165856	SCV000686715	likely benign	Hereditary cancer-predisposing syndrome	2016-07-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000760099	SCV000889880	benign	not provided	2018-03-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000420887	SCV000918348	likely benign	not specified	2018-08-31	criteria provided, single submitter	clinical testing	Variant summary: TP53 c.102C>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.3e-05 in 276916 control chromosomes, but was predominantly found within the Latino subpopulation in the gnomAD database at a frequency of 0.00015. This frequency is nearly 4-fold higher than the maximal expected allele frequency for a pathogenic variant in Li-Fraumeni Syndrome, suggesting the variant is a benign polymorphism in individuals of Latino origin. To our knowledge, no occurrence of c.102C>G in individuals affected with Li-Fraumeni Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Genetic Services Laboratory, University of Chicago	RCV000420887	SCV002066680	likely benign	not specified	2020-11-06	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000165856	SCV002530421	likely benign	Hereditary cancer-predisposing syndrome	2021-05-12	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV000165856	SCV002582295	likely benign	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002288751	SCV002582957	likely benign	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000760099	SCV004141817	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	TP53: BP4, BP7
All of Us Research Program, National Institutes of Health	RCV001081857	SCV004823856	likely benign	Li-Fraumeni syndrome	2023-12-13	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV002288751	SCV005881387	benign	Li-Fraumeni syndrome 1	2025-02-01	criteria provided, single submitter	clinical testing