rs56275308
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000546.6(TP53):c.216C>T(p.Pro72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,613,184 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P72P) 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 -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP53 | NM_000546.6 | c.216C>T | p.Pro72= | synonymous_variant | 4/11 | ENST00000269305.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP53 | ENST00000269305.9 | c.216C>T | p.Pro72= | synonymous_variant | 4/11 | 1 | NM_000546.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000224 AC: 34AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000639 AC: 16AN: 250564Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135758
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1460990Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 726804
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74408
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2014 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 27, 2016 | - - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 26, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 18, 2022 | - - |
Li-Fraumeni syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 01, 2023 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 14, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 30, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Li-Fraumeni syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 18, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 27, 2017 | Variant summary: The TP53 c.216C>T (p.Pro72Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 7/120822 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000602 (6/9970). This frequency is about 15 times the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at