rs749309577
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_000546.6(TP53):āc.516T>Gā(p.Val172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,888 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V172V) has been classified as Likely benign.
Frequency
Consequence
NM_000546.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP53 | NM_000546.6 | c.516T>G | p.Val172= | synonymous_variant | 5/11 | ENST00000269305.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP53 | ENST00000269305.9 | c.516T>G | p.Val172= | synonymous_variant | 5/11 | 1 | NM_000546.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251338Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135866
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461888Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 727246
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Li-Fraumeni syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Apr 03, 2023 | This synonymous variant causes a T>G nucleotide change in exon 5 of the TP53 gene. Splice site prediction tools indicate that this variant may activate a cryptic donor splice site; however, this prediction has not been confirmed in RNA studies. This variant has not been reported in individuals affected with TP53-related disorders in the literature. This variant has been identified in 3/251338 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 26, 2017 | This variant is denoted TP53 c.516T>G at the DNA level. Although this variant is silent at the codinglevel, preserving a Valine at codon 172, it is predicted to cause abnormal splicing through the creation of a new crypticsplice donor site upstream of the natural donor site. However, in the absence of RNA or functional studies, the actualeffect of this variant is unknown. While this variant has not, to our knowledge, been reported as a germline variant ithas been reported as a somatic variant in a neuroblastoma (Hosoi 1994). This variant was not observed in largepopulation cohorts (Lek 2016). The nucleotide which is altered, a thymine (T) at base 516, is not conserved. Based oncurrently available information, it is unclear whether TP53 c.516T>G is a pathogenic or benign variant. We consider itto be a variant of uncertain significance. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 25, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at