ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.97-6C>T (rs35117667)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206386 SCV000261915 benign Li-Fraumeni syndrome 2020-11-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001094499 SCV000407073 benign Li-Fraumeni syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Health, Inc RCV000579891 SCV000686785 benign Hereditary cancer-predisposing syndrome 2015-04-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000581997 SCV000806251 benign not specified 2017-03-27 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282769 SCV001156538 benign none provided 2019-08-10 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000581997 SCV000692098 benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000579891 SCV000788227 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356670 SCV001551905 benign Malignant tumor of breast no assertion criteria provided clinical testing The TP53 c.97-6C>T variant was identified in 1 of 210 proband chromosomes (frequency: 0.00476) from individuals or families with hereditary breast and ovarian cancer (Yorczyk 2015). The variant was also identified in dbSNP (ID: rs35117667) as “With other allele”, ClinVar (as benign by Invitae and likely benign by Illumina), Clinvitae (as benign), LOVD 3.0 (as unknown), and IARC TP53 Database. The variant was not identified in Cosmic, UMD TP52 Mutation Database, or Database of germline p53 mutations. The variant was identified in control databases in 719 of 276982 chromosomes (9 homozygous) at a frequency of 0.002596 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 657 (9 homozygous) of 23962 chromosomes (freq: 0.02742), Other in 3 of 6460 chromosomes (freq: 0.000464), Latino in 51 of 34398 chromosomes (freq: 0.001483), European (Non-Finnish) in 8 of 126616 chromosomes (freq: 0.000063), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The c.97-6C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, 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, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

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