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NM_000546.6(TP53):c.364G>A (p.Val122Met) AND Li-Fraumeni syndrome 1

Germline classification:
Likely benign (1 submission)
Last evaluated:
Jun 2, 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:
RCV001527079.3

Allele description [Variation Report for NM_000546.6(TP53):c.364G>A (p.Val122Met)]

NM_000546.6(TP53):c.364G>A (p.Val122Met)

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.364G>A (p.Val122Met)
HGVS:
  • NC_000017.11:g.7676005C>T
  • NG_017013.2:g.16546G>A
  • NM_000546.6:c.364G>AMANE SELECT
  • NM_001126112.3:c.364G>A
  • NM_001126113.3:c.364G>A
  • NM_001126114.3:c.364G>A
  • NM_001126118.2:c.247G>A
  • NM_001276695.3:c.247G>A
  • NM_001276696.3:c.247G>A
  • NM_001276760.3:c.247G>A
  • NM_001276761.3:c.247G>A
  • NP_000537.3:p.Val122Met
  • NP_000537.3:p.Val122Met
  • NP_001119584.1:p.Val122Met
  • NP_001119585.1:p.Val122Met
  • NP_001119586.1:p.Val122Met
  • NP_001119590.1:p.Val83Met
  • NP_001263624.1:p.Val83Met
  • NP_001263625.1:p.Val83Met
  • NP_001263689.1:p.Val83Met
  • NP_001263690.1:p.Val83Met
  • LRG_321t1:c.364G>A
  • LRG_321:g.16546G>A
  • LRG_321p1:p.Val122Met
  • NC_000017.10:g.7579323C>T
  • NM_000546.4:c.364G>A
  • NM_000546.5(TP53):c.364G>A
  • NM_000546.5:c.364G>A
  • p.V122M
Protein change:
V122M
Links:
dbSNP: rs587781495
NCBI 1000 Genomes Browser:
rs587781495
Molecular consequence:
  • NM_000546.6:c.364G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.364G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.364G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.364G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.247G>A - 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
SCV001737914ClinGen TP53 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1)		Likely benign
(Jun 2, 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, SCV001737914.1

#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 a partially functional variant according to Kato, et al. and there are two additional in vitro assays demonstrating retained function (BS3_Supporting; PMID: 12826609, 30224644, 25584008). 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; Invitae). In summary, TP53 c.364G>A (p.Val122Met) 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_Supporting, BP4, BS2_Supporting. PM2_Supporting should not be considered conflicting evidence as there is sufficient evidence to classify as Likely Benign.

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

Last Updated: Nov 10, 2024