NM_000546.6(TP53):c.380C>T (p.Ser127Phe) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jun 29, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000161024.3

Allele description [Variation Report for NM_000546.6(TP53):c.380C>T (p.Ser127Phe)]

NM_000546.6(TP53):c.380C>T (p.Ser127Phe)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.380C>T (p.Ser127Phe)
Other names:
p.S127F:TCC>TTC
HGVS:
  • NC_000017.11:g.7675232G>A
  • NG_017013.2:g.17319C>T
  • NM_000546.5:c.380C>T
  • NM_000546.6:c.380C>TMANE SELECT
  • NM_001126112.2:c.380C>T
  • NM_001126113.2:c.380C>T
  • NM_001126114.2:c.380C>T
  • NM_001126115.1:c.-17C>T
  • NM_001126116.1:c.-17C>T
  • NM_001126117.1:c.-17C>T
  • NM_001126118.1:c.263C>T
  • NM_001276695.2:c.263C>T
  • NM_001276696.2:c.263C>T
  • NM_001276697.2:c.-98C>T
  • NM_001276698.2:c.-98C>T
  • NM_001276699.2:c.-98C>T
  • NM_001276760.2:c.263C>T
  • NM_001276761.2:c.263C>T
  • NP_000537.3:p.Ser127Phe
  • NP_000537.3:p.Ser127Phe
  • NP_001119584.1:p.Ser127Phe
  • NP_001119585.1:p.Ser127Phe
  • NP_001119586.1:p.Ser127Phe
  • NP_001119590.1:p.Ser88Phe
  • NP_001263624.1:p.Ser88Phe
  • NP_001263625.1:p.Ser88Phe
  • NP_001263689.1:p.Ser88Phe
  • NP_001263690.1:p.Ser88Phe
  • LRG_321t1:c.380C>T
  • LRG_321t2:c.380C>T
  • LRG_321t3:c.380C>T
  • LRG_321t4:c.380C>T
  • LRG_321t5:c.-17C>T
  • LRG_321t6:c.-17C>T
  • LRG_321t7:c.-17C>T
  • LRG_321t8:c.263C>T
  • LRG_321:g.17319C>T
  • LRG_321:p.Ser127Phe
  • LRG_321p1:p.Ser127Phe
  • LRG_321p3:p.Ser127Phe
  • LRG_321p4:p.Ser127Phe
  • LRG_321p8:p.Ser88Phe
  • NC_000017.10:g.7578550G>A
  • NM_000546.4:c.380C>T
  • P04637:p.Ser127Phe
Protein change:
S127F
Links:
UniProtKB: P04637#VAR_005867; dbSNP: rs730881999
NCBI 1000 Genomes Browser:
rs730881999
Molecular consequence:
  • NM_001126115.1:c.-17C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001126116.1:c.-17C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001126117.1:c.-17C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276697.2:c.-98C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276698.2:c.-98C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276699.2:c.-98C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.5:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000546.6:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.2:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.2:c.380C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.1:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.2:c.263C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000211743GeneDxcriteria provided, single submitter
Likely pathogenic
(Jun 29, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000211743.13

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted TP53 c.380C>T at the cDNA level, p.Ser127Phe (S127F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). TP53 Ser127Phe has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant, but has been reported as a somatic variant in acute lymphoblastic leukemia, melanoma, and other tumors and cell lines (Daniotti 2004, Hof 2011, COSMIC). This variant has demonstrated reduced transcriptional activation for multiple p53 response elements (Dekairelle 2005, Bally 2015) and is reported as having non-functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003). TP53 Ser127Phe was not observed in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Bode 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, we consider TP53 Ser127Phe to be a likely pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

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