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NM_000546.6(TP53):c.376-1G>T AND Li-Fraumeni syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 1, 2021
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:
RCV001882697.4

Allele description [Variation Report for NM_000546.6(TP53):c.376-1G>T]

NM_000546.6(TP53):c.376-1G>T

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.376-1G>T
HGVS:
  • NC_000017.11:g.7675237C>A
  • NG_017013.2:g.17314G>T
  • NM_000546.6:c.376-1G>TMANE SELECT
  • NM_001126112.3:c.376-1G>T
  • NM_001126113.3:c.376-1G>T
  • NM_001126114.3:c.376-1G>T
  • NM_001126115.2:c.-22G>T
  • NM_001126116.2:c.-22G>T
  • NM_001126117.2:c.-22G>T
  • NM_001126118.2:c.259-1G>T
  • NM_001276695.3:c.259-1G>T
  • NM_001276696.3:c.259-1G>T
  • NM_001276697.3:c.-103G>T
  • NM_001276698.3:c.-103G>T
  • NM_001276699.3:c.-103G>T
  • NM_001276760.3:c.259-1G>T
  • NM_001276761.3:c.259-1G>T
  • NM_001407262.1:c.376-1G>T
  • NM_001407263.1:c.259-1G>T
  • NM_001407264.1:c.376-1G>T
  • NM_001407265.1:c.259-1G>T
  • NM_001407266.1:c.376-1G>T
  • NM_001407267.1:c.259-1G>T
  • NM_001407268.1:c.376-1G>T
  • NM_001407269.1:c.259-1G>T
  • NM_001407270.1:c.376-1G>T
  • NM_001407271.1:c.259-1G>T
  • LRG_321t5:c.-22G>T
  • LRG_321t6:c.-22G>T
  • LRG_321t7:c.-22G>T
  • LRG_321:g.17314G>T
  • NC_000017.10:g.7578555C>A
  • NM_000546.4:c.376-1G>T
  • NM_001126115.1:c.-22G>T
  • NM_001126116.1:c.-22G>T
  • NM_001126117.1:c.-22G>T
Links:
dbSNP: rs868137297
NCBI 1000 Genomes Browser:
rs868137297
Molecular consequence:
  • NM_001126115.2:c.-22G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001126116.2:c.-22G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001126117.2:c.-22G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276697.3:c.-103G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276698.3:c.-103G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276699.3:c.-103G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.6:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001126112.3:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001126113.3:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001126114.3:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001126118.2:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001276695.3:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001276696.3:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001276760.3:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001276761.3:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407262.1:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407263.1:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407264.1:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407265.1:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407266.1:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407267.1:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407268.1:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407269.1:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407270.1:c.376-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001407271.1:c.259-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
Functional consequence:
sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002242785Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 1, 2021) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers.

Hettmer S, Archer NM, Somers GR, Novokmet A, Wagers AJ, Diller L, Rodriguez-Galindo C, Teot LA, Malkin D.

Cancer. 2014 Apr 1;120(7):1068-75. doi: 10.1002/cncr.28507. Epub 2013 Dec 30. Erratum in: Cancer. 2014 Jun 15;120(12):1910.

PubMed [citation]
PMID:
24382691
PMCID:
PMC4173134

Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.

Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, Gallinger B, Naumer A, Kohlmann W, Novokmet A, Tabori U, Tijerin M, Greer ML, Finlay JL, Schiffman JD, Malkin D.

Lancet Oncol. 2016 Sep;17(9):1295-305. doi: 10.1016/S1470-2045(16)30249-2. Epub 2016 Aug 5.

PubMed [citation]
PMID:
27501770
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002242785.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1210292). Disruption of this splice site has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 24382691, 27501770, 29752822, 32930885; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 4 of the TP53 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432).

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

Last Updated: Sep 29, 2024