17-7674237-G-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_000546.6(TP53):c.726C>G(p.Cys242Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000546.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461814Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727220
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Li-Fraumeni syndrome Pathogenic:1
This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 242 of the TP53 protein (p.Cys242Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with early onset breast cancer (PMID: 32959997). ClinVar contains an entry for this variant (Variation ID: 376580). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. This variant disrupts the p.Cys242 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8164043, 9364015, 19930417, 20407015, 21343334, 25896519, 27276934). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at