17-7687396-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000546.6(TP53):c.-48G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 398,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000546.6 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000244 AC: 6AN: 246342Hom.: 0 Cov.: 0 AF XY: 0.0000320 AC XY: 4AN XY: 124822
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74460
ClinVar
Submissions by phenotype
not specified Uncertain:1
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not provided Uncertain:1
This variant is denoted TP53 c.-48G>A, and describes a nucleotide substitution in the 5Â’ untranslated region (UTR) 48 base pairs upstream of the TP53 ATG translational start site, which is located in exon 2. The surrounding sequence, with the base that is substituted in braces, is CGGT[G/A]ACAC. While multiple in silico splicing models predict the creation of a new cryptic splice donor site upstream of the natural splice donor site in intron 1, possibly leading to abnormal gene splicing, it is unknown whether this change will affect the promoter and/or protein translation. This variant does not appear to affect the start codon or the Kozak translational consensus sequence in exon 2 and has not, to our knowledge, been published in the literature as pathogenic or benign. TP53 c.-48G>A was not observed at a significant allele frequency in 1000 Genomes. The guanine (G) nucleotide that is altered is not conserved. Based on currently available evidence, it is unclear whether TP53 c.-48G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at