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NM_000546.6(TP53):c.344A>G (p.His115Arg) AND Li-Fraumeni syndrome 1

Germline classification:
Likely benign (1 submission)
Last evaluated:
Apr 12, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001527098.3

Allele description [Variation Report for NM_000546.6(TP53):c.344A>G (p.His115Arg)]

NM_000546.6(TP53):c.344A>G (p.His115Arg)

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.344A>G (p.His115Arg)
Other names:
p.H115R:CAT>CGT
HGVS:
  • NC_000017.11:g.7676025T>C
  • NG_017013.2:g.16526A>G
  • NM_000546.6:c.344A>GMANE SELECT
  • NM_001126112.3:c.344A>G
  • NM_001126113.3:c.344A>G
  • NM_001126114.3:c.344A>G
  • NM_001126118.2:c.227A>G
  • NM_001276695.3:c.227A>G
  • NM_001276696.3:c.227A>G
  • NM_001276760.3:c.227A>G
  • NM_001276761.3:c.227A>G
  • NP_000537.3:p.His115Arg
  • NP_000537.3:p.His115Arg
  • NP_001119584.1:p.His115Arg
  • NP_001119585.1:p.His115Arg
  • NP_001119586.1:p.His115Arg
  • NP_001119590.1:p.His76Arg
  • NP_001263624.1:p.His76Arg
  • NP_001263625.1:p.His76Arg
  • NP_001263689.1:p.His76Arg
  • NP_001263690.1:p.His76Arg
  • LRG_321t1:c.344A>G
  • LRG_321t2:c.344A>G
  • LRG_321:g.16526A>G
  • LRG_321p1:p.His115Arg
  • NC_000017.10:g.7579343T>C
  • NM_000546.4:c.344A>G
  • NM_000546.5:c.344A>G
  • NM_001126112.2(TP53):c.344A>G
  • p.His115Arg
Protein change:
H115R
Links:
dbSNP: rs730881996
NCBI 1000 Genomes Browser:
rs730881996
Molecular consequence:
  • NM_000546.6:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001737943ClinGen TP53 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1)		Likely benign
(Apr 12, 2021) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen TP53 Variant Curation Expert Panel, ClinGen, SCV001737943.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). Transactivation assays show [retained/supertransactivation] function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, TP53 c.344A>G (p.His115Arg) 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: PM2_Supporting, BS3, BP4. In this case, PM2_Supporting should not be applied as there is sufficient evidence codes for variant to meet Likely Benign classification.

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

Last Updated: Nov 10, 2024