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NM_000546.6(TP53):c.375+1G>C AND Li-Fraumeni syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 28, 2022
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:
RCV000822481.5

Allele description [Variation Report for NM_000546.6(TP53):c.375+1G>C]

NM_000546.6(TP53):c.375+1G>C

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.375+1G>C
HGVS:
  • NC_000017.11:g.7675993C>G
  • NG_017013.2:g.16558G>C
  • NM_000546.6:c.375+1G>CMANE SELECT
  • NM_001126112.3:c.375+1G>C
  • NM_001126113.3:c.375+1G>C
  • NM_001126114.3:c.375+1G>C
  • NM_001126118.2:c.258+1G>C
  • NM_001276695.3:c.258+1G>C
  • NM_001276696.3:c.258+1G>C
  • NM_001276760.3:c.258+1G>C
  • NM_001276761.3:c.258+1G>C
  • NM_001407262.1:c.375+1G>C
  • NM_001407263.1:c.258+1G>C
  • NM_001407264.1:c.375+1G>C
  • NM_001407265.1:c.258+1G>C
  • NM_001407266.1:c.375+1G>C
  • NM_001407267.1:c.258+1G>C
  • NM_001407268.1:c.375+1G>C
  • NM_001407269.1:c.258+1G>C
  • NM_001407270.1:c.375+1G>C
  • NM_001407271.1:c.258+1G>C
  • LRG_321t1:c.375+1G>C
  • LRG_321:g.16558G>C
  • NC_000017.10:g.7579311C>G
  • NM_000546.5:c.375+1G>C
Links:
dbSNP: rs1567555445
NCBI 1000 Genomes Browser:
rs1567555445
Molecular consequence:
  • NM_000546.6:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001126112.3:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001126113.3:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001126114.3:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001126118.2:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001276695.3:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001276696.3:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001276760.3:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001276761.3:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407262.1:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407263.1:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407264.1:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407265.1:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407266.1:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407267.1:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407268.1:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407269.1:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407270.1:c.375+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407271.1:c.258+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000963287Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 28, 2022) 		germlineclinical testing

PubMed (5)
[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

Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.

Frebourg T, Barbier N, Yan YX, Garber JE, Dreyfus M, Fraumeni J Jr, Li FP, Friend SH.

Am J Hum Genet. 1995 Mar;56(3):608-15.

PubMed [citation]
PMID:
7887414
PMCID:
PMC1801151

Increased access to TP53 analysis through breast cancer multi-gene panels: clinical considerations.

Azzollini J, Mariani M, Peissel B, Manoukian S.

Fam Cancer. 2018 Jul;17(3):317-319. doi: 10.1007/s10689-017-0020-z. No abstract available.

PubMed [citation]
PMID:
28681140
PMCID:
PMC5999151
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000963287.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

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: 664392). Disruption of this splice site has been observed in individuals with Li-Fraumeni syndrome (PMID: 7887414, 28681140; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor 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: May 7, 2024