rs1555525703
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000546.6(TP53):c.672+2T>G variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_000546.6 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Li-Fraumeni syndrome Pathogenic:2
The following ACMG criteria was used: PVS1; PM2_SUP; PS4_SUP -
For these reasons, this variant has been classified as Pathogenic. RNA analysis provides insufficient evidence to determine the effect of this variant on TP53 splicing (Invitae). ClinVar contains an entry for this variant (Variation ID: 635389). Disruption of this splice site has been observed in individuals with clinical features of Li-Fraumeni syndrome (PMID: 14656244, 19556618, 23409989, 29324801). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the TP53 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). -
not provided Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at