ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.782+6G>A

gnomAD frequency: 0.00001  dbSNP: rs1008479744
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001707837 SCV000727201 likely benign not provided 2020-09-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000633399 SCV000754621 uncertain significance Li-Fraumeni syndrome 2024-08-20 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the TP53 gene. It does not directly change the encoded amino acid sequence of the TP53 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 515187). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Color Diagnostics, LLC DBA Color Health RCV001176035 SCV001339850 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-08 criteria provided, single submitter clinical testing This variant causes a G to A nucleotide substitution at the +6 position of intron 7 of the TP53 gene. To our knowledge, RNA studies have not been reported for this variant. This variant has not been reported in individuals affected with TP53-related disorders in the literature. This variant has been identified in 1/251366 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV000633399 SCV004831584 uncertain significance Li-Fraumeni syndrome 2023-10-02 criteria provided, single submitter clinical testing This variant causes a G to A nucleotide substitution at the +6 position of intron 7 of the TP53 gene. To our knowledge, RNA studies have not been reported for this variant. This variant has not been reported in individuals affected with TP53-related disorders in the literature. This variant has been identified in 1/251366 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782469 SCV005394150 uncertain significance not specified 2024-09-03 criteria provided, single submitter clinical testing Variant summary: TP53 c.782+6G>A 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. Consensus agreement among computation 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 4e-06 in 251366 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.782+6G>A in individuals affected with Li-Fraumeni Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 515187). Based on the evidence outlined above, the variant was classified as uncertain significance.

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.