ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.250G>A (p.Ala84Thr) (rs587781307)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel,ClinGen RCV000462026 SCV001429622 likely benign Li-Fraumeni syndrome 2020-08-11 reviewed by expert panel curation This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). Transactivation assays show retained function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). In summary, TP53 c.250G>A (p.Ala84Thr) meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the TP53 Expert Panel: BP4 and BS3.
Ambry Genetics RCV000129026 SCV000172931 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-08 criteria provided, single submitter clinical testing The p.A84T variant (also known as c.250G>A), located in coding exon 3 of the TP53 gene, results from a G to A substitution at nucleotide position 250. The alanine at codon 84 is replaced by threonine, an amino acid with similar properties. This variant was shown to have transactivation capabilities similar to wild type in yeast based functional studies (Kato S et al. Proc. Natl. Acad. Sci. U.S.A., 2003 Jul;100:8424-9). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl RCV000409852 SCV000489003 uncertain significance Li-Fraumeni syndrome 1 2016-08-05 criteria provided, single submitter clinical testing
Invitae RCV000462026 SCV000545271 uncertain significance Li-Fraumeni syndrome 2020-10-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 84 of the TP53 protein (p.Ala84Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 140833). This variant has been reported not to substantially affect TP53 protein function (PMID: 12826609). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759372 SCV000888663 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129026 SCV000908798 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-25 criteria provided, single submitter clinical testing

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