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NM_000546.6(TP53):c.1093C>T (p.His365Tyr) AND Malignant tumor of breast

Germline classification:
Uncertain significance (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001358057.3

Allele description [Variation Report for NM_000546.6(TP53):c.1093C>T (p.His365Tyr)]

NM_000546.6(TP53):c.1093C>T (p.His365Tyr)

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.1093C>T (p.His365Tyr)
HGVS:
  • NC_000017.11:g.7670616G>A
  • NG_017013.2:g.21935C>T
  • NM_000546.6:c.1093C>TMANE SELECT
  • NM_001126112.3:c.1093C>T
  • NM_001126113.3:c.*112C>T
  • NM_001126114.3:c.*200C>T
  • NM_001126115.1:c.697C>T
  • NM_001126115.2:c.697C>T
  • NM_001126116.1:c.*200C>T
  • NM_001126116.2:c.*200C>T
  • NM_001126117.1:c.*112C>T
  • NM_001126117.2:c.*112C>T
  • NM_001126118.2:c.976C>T
  • NM_001276695.3:c.*112C>T
  • NM_001276696.3:c.*200C>T
  • NM_001276697.3:c.616C>T
  • NM_001276698.3:c.*200C>T
  • NM_001276699.3:c.*112C>T
  • NM_001276760.3:c.976C>T
  • NM_001276761.3:c.976C>T
  • NP_000537.3:p.His365Tyr
  • NP_000537.3:p.His365Tyr
  • NP_001119584.1:p.His365Tyr
  • NP_001119587.1:p.His233Tyr
  • NP_001119590.1:p.His326Tyr
  • NP_001263626.1:p.His206Tyr
  • NP_001263689.1:p.His326Tyr
  • NP_001263690.1:p.His326Tyr
  • LRG_321t1:c.1093C>T
  • LRG_321:g.21935C>T
  • LRG_321p1:p.His365Tyr
  • NC_000017.10:g.7573934G>A
  • NC_000017.9:g.7514659G>A
  • NM_000546.4:c.1093C>T
  • NM_000546.5(TP53):c.1093C>T
  • NM_000546.5:c.1093C>T
  • NM_000546.6:c.1093C>T
  • P04637:p.His365Tyr
  • p.H365Y
Protein change:
H206Y
Links:
UniProtKB: P04637#VAR_045568; dbSNP: rs267605075
NCBI 1000 Genomes Browser:
rs267605075
Molecular consequence:
  • NM_001126113.3:c.*112C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126114.3:c.*200C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126116.2:c.*200C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126117.2:c.*112C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276695.3:c.*112C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276696.3:c.*200C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276698.3:c.*200C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276699.3:c.*112C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000546.6:c.1093C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.1093C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.697C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.976C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.616C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.976C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.976C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Malignant tumor of breast
Synonyms:
Malignant breast neoplasm; Cancer breast
Identifiers:
MONDO: MONDO:0007254; MedGen: C0006142

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001553701Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Uncertain significanceunknownclinical testing

Help

Summary from all submissions

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

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001553701.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The TP53 p.His365Tyr variant was identified in 2 of 246 proband chromosomes (frequency: 0.008) from individuals or families with lung cancer or soft tissue sarcoma (Hayes 1999, Hwang 2003). The variant was also identified in dbSNP (ID: rs267605075) as "With Uncertain significance allele", ClinVar (classified as uncertain significance by Ambry Genetics and True Health Diagnostics), Cosmic (1x in Stomach tissue), and in IARC TP53 Database (3x). The variant was not identified in COGR, or LOVD 3.0 databases. The variant was identified in control databases in 1 of 244474 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 1 of 110730 chromosomes (freq: 0.000009), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.His365 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In yeast-based systematic analysis the variant was classified as a partial deficiency allele based on its ability to transactivate a set of human target sequences and showed ~25% of wild-type activity toward at least one response element (Monti 2007, Monti 2011). In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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

Last Updated: Oct 13, 2024