NM_000546.5:c.370T>G (p.Cys124Gly) is a missense variant in TP53 exon 4, absent from gnomAD v2.1 and v4.1 (PM2_Supporting met; 1 point).
gnomad_v2 ↗ gnomad_v4 ↗In silico analysis per TP53 VCEP assigns PP3_Moderate: aGVGD Class C65 and BayesDel 0.217 (≥0.16), with no predicted splicing effect (SpliceAI max delta 0.04) (2 points).
spliceai ↗No functional evidence is applicable per the TP53 VCEP Functional-worksheet, which assigns C124G a code of 'No evidence' due to mixed assay results: Kato partially functional, Giacomelli LOF, Kotler noLOF.
The variant has been observed 6 times in somatic cancers (COSMIC COSV52680549) but is not listed in cancerhotspots.org as a statistically significant hotspot, and codon 124 is not among the VCEP-defined PM1 hotspot codons.
cspec ↗No proband-level phenotype, cosegregation, de novo, or case-control data are available for this variant. ClinVar reports a single submitter classification of Uncertain significance.
clinvar ↗Total Tavtigian points: PM2_Supporting (1) + PP3_Moderate (2) = 3 points, falling within the TP53 VCEP VUS range (-1 to 5 points). The variant is classified as Uncertain Significance.
cspec ↗
