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NM_000546.6(TP53):c.949C>A (p.Gln317Lys) AND Li-Fraumeni syndrome 1

Germline classification:
Likely benign (1 submission)
Last evaluated:
Aug 4, 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:
RCV001723805.3

Allele description [Variation Report for NM_000546.6(TP53):c.949C>A (p.Gln317Lys)]

NM_000546.6(TP53):c.949C>A (p.Gln317Lys)

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.949C>A (p.Gln317Lys)
Other names:
NM_000546.5(TP53):c.949C>A
HGVS:
  • NC_000017.11:g.7673579G>T
  • NG_017013.2:g.18972C>A
  • NM_000546.6:c.949C>AMANE SELECT
  • NM_001126112.3:c.949C>A
  • NM_001126113.3:c.949C>A
  • NM_001126114.3:c.949C>A
  • NM_001126115.2:c.553C>A
  • NM_001126116.2:c.553C>A
  • NM_001126117.2:c.553C>A
  • NM_001126118.2:c.832C>A
  • NM_001276695.3:c.832C>A
  • NM_001276696.3:c.832C>A
  • NM_001276697.3:c.472C>A
  • NM_001276698.3:c.472C>A
  • NM_001276699.3:c.472C>A
  • NM_001276760.3:c.832C>A
  • NM_001276761.3:c.832C>A
  • NP_000537.3:p.Gln317Lys
  • NP_000537.3:p.Gln317Lys
  • NP_001119584.1:p.Gln317Lys
  • NP_001119585.1:p.Gln317Lys
  • NP_001119586.1:p.Gln317Lys
  • NP_001119587.1:p.Gln185Lys
  • NP_001119588.1:p.Gln185Lys
  • NP_001119589.1:p.Gln185Lys
  • NP_001119590.1:p.Gln278Lys
  • NP_001263624.1:p.Gln278Lys
  • NP_001263625.1:p.Gln278Lys
  • NP_001263626.1:p.Gln158Lys
  • NP_001263627.1:p.Gln158Lys
  • NP_001263628.1:p.Gln158Lys
  • NP_001263689.1:p.Gln278Lys
  • NP_001263690.1:p.Gln278Lys
  • LRG_321t1:c.949C>A
  • LRG_321:g.18972C>A
  • LRG_321p1:p.Gln317Lys
  • NC_000017.10:g.7576897G>T
  • NM_000546.4:c.949C>A
  • NM_000546.5:c.949C>A
  • P04637:p.Gln317Lys
Protein change:
Q158K
Links:
UniProtKB: P04637#VAR_045500; dbSNP: rs764735889
NCBI 1000 Genomes Browser:
rs764735889
Molecular consequence:
  • NM_000546.6:c.949C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.949C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.949C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.949C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.553C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.553C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.553C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.832C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.832C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.832C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.472C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.472C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.472C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.832C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.832C>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
SCV001949921ClinGen TP53 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1.2)		Likely benign
(Aug 4, 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, SCV001949921.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Transactivation assays show retained 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). 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.949C>A (p.Gln317Lys) 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: BS3, BS2_supporting, BP4.

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

Last Updated: Oct 20, 2024