NM_000546.6(TP53):c.493C>T (p.Gln165Ter) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000633373.7

Allele description [Variation Report for NM_000546.6(TP53):c.493C>T (p.Gln165Ter)]

NM_000546.6(TP53):c.493C>T (p.Gln165Ter)

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.493C>T (p.Gln165Ter)

Other names:

p.Q165*:CAG>TAG

HGVS:

NC_000017.11:g.7675119G>A
NG_017013.2:g.17432C>T
NM_000546.6:c.493C>TMANE SELECT
NM_001126112.3:c.493C>T
NM_001126113.3:c.493C>T
NM_001126114.3:c.493C>T
NM_001126115.2:c.97C>T
NM_001126116.2:c.97C>T
NM_001126117.2:c.97C>T
NM_001126118.2:c.376C>T
NM_001276695.3:c.376C>T
NM_001276696.3:c.376C>T
NM_001276697.3:c.16C>T
NM_001276698.3:c.16C>T
NM_001276699.3:c.16C>T
NM_001276760.3:c.376C>T
NM_001276761.3:c.376C>T
NP_000537.3:p.Gln165Ter
NP_000537.3:p.Gln165Ter
NP_001119584.1:p.Gln165Ter
NP_001119585.1:p.Gln165Ter
NP_001119586.1:p.Gln165Ter
NP_001119587.1:p.Gln33Ter
NP_001119588.1:p.Gln33Ter
NP_001119589.1:p.Gln33Ter
NP_001119590.1:p.Gln126Ter
NP_001119590.1:p.Gln126Ter
NP_001263624.1:p.Gln126Ter
NP_001263625.1:p.Gln126Ter
NP_001263626.1:p.Gln6Ter
NP_001263627.1:p.Gln6Ter
NP_001263628.1:p.Gln6Ter
NP_001263689.1:p.Gln126Ter
NP_001263690.1:p.Gln126Ter
LRG_321t1:c.493C>T
LRG_321t8:c.376C>T
LRG_321:g.17432C>T
LRG_321p1:p.Gln165Ter
LRG_321p8:p.Gln126Ter
NC_000017.10:g.7578437G>A
NM_000546.4:c.493C>T
NM_000546.5:c.493C>T
NM_001126118.1:c.376C>T

Protein change:

Q126*

Links:

dbSNP: rs730882001

NCBI 1000 Genomes Browser:

rs730882001

Molecular consequence:

NM_000546.6:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126112.3:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126113.3:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126114.3:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126115.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126116.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126117.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126118.2:c.376C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276695.3:c.376C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276696.3:c.376C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276697.3:c.16C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276698.3:c.16C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276699.3:c.16C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276760.3:c.376C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276761.3:c.376C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Li-Fraumeni syndrome (LFS)
Synonyms:: Sarcoma family syndrome of Li and Fraumeni
Identifiers:: MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000754595	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20522432, 26681312, 29753700, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754595

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 3, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.

Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ.

J Med Genet. 2010 Jun;47(6):421-8. doi: 10.1136/jmg.2009.073429.

PubMed [citation]

PMID:: 20522432

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2.

PubMed [citation]

PMID:: 26681312
PMCID:: PMC4985612

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000754595.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gln165*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer and medulloblastoma (PMID: 26681312, 29753700). ClinVar contains an entry for this variant (Variation ID: 182930). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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