NM_000546.5(TP53):c.145G>C (p.Asp49His) AND Li-Fraumeni syndrome 1

Clinical significance:Likely benign (Last evaluated: May 6, 2021)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000410497.3

Allele description [Variation Report for NM_000546.5(TP53):c.145G>C (p.Asp49His)]

NM_000546.5(TP53):c.145G>C (p.Asp49His)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.145G>C (p.Asp49His)
HGVS:
  • NC_000017.11:g.7676224C>G
  • NG_017013.2:g.16327G>C
  • NM_000546.5:c.145G>C
  • NM_001126112.2:c.145G>C
  • NM_001126113.2:c.145G>C
  • NM_001126114.2:c.145G>C
  • NM_001126118.1:c.28G>C
  • NM_001276695.2:c.28G>C
  • NM_001276696.2:c.28G>C
  • NM_001276760.2:c.28G>C
  • NM_001276761.2:c.28G>C
  • NP_000537.3:p.Asp49His
  • NP_001119584.1:p.Asp49His
  • NP_001119585.1:p.Asp49His
  • NP_001119586.1:p.Asp49His
  • NP_001119590.1:p.Asp10His
  • NP_001263624.1:p.Asp10His
  • NP_001263625.1:p.Asp10His
  • NP_001263689.1:p.Asp10His
  • NP_001263690.1:p.Asp10His
  • LRG_321t1:c.145G>C
  • LRG_321t2:c.145G>C
  • LRG_321t3:c.145G>C
  • LRG_321t4:c.145G>C
  • LRG_321t8:c.28G>C
  • LRG_321:g.16327G>C
  • LRG_321:p.Asp49His
  • LRG_321p1:p.Asp49His
  • LRG_321p3:p.Asp49His
  • LRG_321p4:p.Asp49His
  • LRG_321p8:p.Asp10His
  • NC_000017.10:g.7579542C>G
  • NM_000546.4:c.145G>C
  • NM_001126112.2(TP53):c.145G>C
  • P04637:p.Asp49His
  • p.D49H
Protein change:
D10H
Links:
UniProtKB: P04637#VAR_044571; dbSNP: rs587780728
NCBI 1000 Genomes Browser:
rs587780728
Molecular consequence:
  • NM_000546.5:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.2:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.2:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.1:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome 1 (LFS)
Synonyms:
Li-Fraumeni syndrome 3
Identifiers:
Gene: 553989; MONDO: MONDO:0007903; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000488754Counsylcriteria provided, single submitter
Uncertain significance
(Jun 7, 2016)
unknownclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV001282023Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001737934ClinGen TP53 Variant Curation Expert Panel,ClinGenreviewed by expert panel
Likely benign
(May 6, 2021)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Interaction between replication protein A and p53 is disrupted after UV damage in a DNA repair-dependent manner.

Abramova NA, Russell J, Botchan M, Li R.

Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7186-91.

PubMed [citation]
PMID:
9207066
PMCID:
PMC23787

Loss of transactivation and transrepression function, and not RPA binding, alters growth suppression by p53.

Leiter LM, Chen J, Marathe T, Tanaka M, Dutta A.

Oncogene. 1996 Jun 20;12(12):2661-8.

PubMed [citation]
PMID:
8700525
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000488754.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV001282023.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From ClinGen TP53 Variant Curation Expert Panel,ClinGen, SCV001737934.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributor). In summary, TP53 c.125G>C (p.D49H) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BP4, BS2_Supporting.

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

Last Updated: Jun 23, 2021

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