17-7676154-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000546.6(TP53):āc.215C>Gā(p.Pro72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,613,582 control chromosomes in the GnomAD database, including 411,964 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P72A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000546.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP53 | NM_000546.6 | c.215C>G | p.Pro72Arg | missense_variant | 4/11 | ENST00000269305.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP53 | ENST00000269305.9 | c.215C>G | p.Pro72Arg | missense_variant | 4/11 | 1 | NM_000546.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.627 AC: 95293AN: 151904Hom.: 31786 Cov.: 31
GnomAD3 exomes AF: 0.668 AC: 167398AN: 250534Hom.: 57557 AF XY: 0.664 AC XY: 90173AN XY: 135746
GnomAD4 exome AF: 0.716 AC: 1046941AN: 1461558Hom.: 380188 Cov.: 80 AF XY: 0.710 AC XY: 516401AN XY: 727064
GnomAD4 genome ? AF: 0.627 AC: 95285AN: 152024Hom.: 31776 Cov.: 31 AF XY: 0.625 AC XY: 46413AN XY: 74294
ClinVar
Submissions by phenotype
not specified Benign:7Other:1
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 05, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Li-Fraumeni syndrome 1 Uncertain:1Benign:5
Uncertain significance, no assertion criteria provided | clinical testing | Pathway Genomics | Jul 24, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 18, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | IntelligeneCG | Aug 18, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:3
Benign, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 30, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 17719241, 22289634, 23729685, 22703879, 18990008, 22524816, 20128691, 12459171, 19657731, 15138483, 21323870, 18426989, 15183530, 20587514, 18256523, 19789321, 15131588, 19837266, 18567547, 23210739, 22189267, 21038427, 20019240, 23073555, 20939739, 19357867, 19521721, 20886596, 21931130, 21454683, 21814224, 22336889, 19542078, 16258005, 11983757, 19657586, 11844595, 22367371, 21245379, 9891044, 17403527, 18583979, 12567188, 19171829, 19165225, 19639206, 21124037, 23207172, 21778786, 24728327, 21283750, 22545084, 24747975, 12826609, 19470478, 8625447, 23793604, 27153395, 25896519, 15609317, 23683469, 9607760) - |
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 05, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 18, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2014 | This alteration is classified as 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. - |
Li-Fraumeni syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Hereditary breast ovarian cancer syndrome Benign:2
Benign, criteria provided, single submitter | research | Genetics Program, Instituto Nacional de Cancer | Nov 01, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | National Health Laboratory Service, Universitas Academic Hospital and University of the Free State | Apr 19, 2022 | - - |
Lip and oral cavity carcinoma Pathogenic:1
Pathogenic, no assertion criteria provided | research | Institute of Medical Sciences, Banaras Hindu University | Apr 30, 2019 | - - |
Choroid plexus papilloma;C0235974:Carcinoma of pancreas;C0346153:Familial cancer of breast;C0346629:Colorectal cancer;C0585442:Bone osteosarcoma;C1835398:Li-Fraumeni syndrome 1;C1859972:Adrenocortical carcinoma, hereditary;C2239176:Hepatocellular carcinoma;C2750850:Glioma susceptibility 1;C2931822:Nasopharyngeal carcinoma;C3553606:Basal cell carcinoma, susceptibility to, 7;C4748488:Bone marrow failure syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 20, 2021 | - - |
CODON 72 POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Oct 01, 2009 | - - |
Acute myeloid leukemia Benign:1
Benign, no assertion criteria provided | clinical testing | Dr. Afia Zoology Lab, University of Education | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at