ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.97-9C>T

gnomAD frequency: 0.00011  dbSNP: rs202217267
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000161046 SCV000211776 benign not specified 2014-06-10 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.
Invitae RCV001079867 SCV000253318 likely benign Li-Fraumeni syndrome 2022-11-03 criteria provided, single submitter clinical testing
Counsyl RCV000410371 SCV000488528 uncertain significance Li-Fraumeni syndrome 1 2016-04-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000195920 SCV000602284 likely benign not provided 2020-04-14 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000580612 SCV000686786 likely benign Hereditary cancer-predisposing syndrome 2016-04-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000161046 SCV001370686 benign not specified 2020-05-26 criteria provided, single submitter clinical testing Variant summary: TP53 c.97-9C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.00014 in 250376 control chromosomes. The observed variant frequency is approximately 3.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Li-Fraumeni Syndrome phenotype (4e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.97-9C>T in individuals affected with Li-Fraumeni Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=3; VUS, n=1). Based on the evidence outlined above, the variant was classified as benign.
Genetic Services Laboratory, University of Chicago RCV000161046 SCV002070160 likely benign not specified 2020-02-26 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000580612 SCV002532732 benign Hereditary cancer-predisposing syndrome 2021-03-24 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000161046 SCV002551136 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000410371 SCV004017841 likely benign Li-Fraumeni syndrome 1 2023-04-11 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000410371 SCV001552654 likely benign Li-Fraumeni syndrome 1 no assertion criteria provided clinical testing The TP53 c.97-9C>T variant was not identified in the literature nor was it identified in the LOVD 3.0 or UMD-LSDB databases. The variant was identified in dbSNP (ID: rs202217267) as "With other allele" and ClinVar (classified as benign by GeneDx; as likely benign by Invitae, Color and Quest Diagnostics Nichols Institute San Juan Capistrano; and as uncertain significance by Counsyl). The variant was identified in control databases in 35 of 276116 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 32 of 126596 chromosomes (freq: 0.0003, increasing the likelihood this could be a low frequency benign variant), Latino in 2 of 34398 chromosomes (freq: 0.00006), and Finnish in 1 of 24966 chromosomes (freq: 0.00004), while it was not observed in the African, Other, Ashkenazi Jewish, East Asian, or South Asian populations. The c.97-9C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. Positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing; however, 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.