NM_000546.6(TP53):c.935C>G (p.Thr312Ser) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Nov 3, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000213063.17

Allele description [Variation Report for NM_000546.6(TP53):c.935C>G (p.Thr312Ser)]

NM_000546.6(TP53):c.935C>G (p.Thr312Ser)

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.935C>G (p.Thr312Ser)

Other names:

p.T312S:ACC>AGC

HGVS:

NC_000017.11:g.7673593G>C
NG_017013.2:g.18958C>G
NM_000546.6:c.935C>GMANE SELECT
NM_001126112.3:c.935C>G
NM_001126113.3:c.935C>G
NM_001126114.3:c.935C>G
NM_001126115.2:c.539C>G
NM_001126116.2:c.539C>G
NM_001126117.2:c.539C>G
NM_001126118.2:c.818C>G
NM_001276695.3:c.818C>G
NM_001276696.3:c.818C>G
NM_001276697.3:c.458C>G
NM_001276698.3:c.458C>G
NM_001276699.3:c.458C>G
NM_001276760.3:c.818C>G
NM_001276761.3:c.818C>G
NP_000537.3:p.Thr312Ser
NP_000537.3:p.Thr312Ser
NP_001119584.1:p.Thr312Ser
NP_001119585.1:p.Thr312Ser
NP_001119586.1:p.Thr312Ser
NP_001119587.1:p.Thr180Ser
NP_001119588.1:p.Thr180Ser
NP_001119589.1:p.Thr180Ser
NP_001119590.1:p.Thr273Ser
NP_001263624.1:p.Thr273Ser
NP_001263625.1:p.Thr273Ser
NP_001263626.1:p.Thr153Ser
NP_001263627.1:p.Thr153Ser
NP_001263628.1:p.Thr153Ser
NP_001263689.1:p.Thr273Ser
NP_001263690.1:p.Thr273Ser
LRG_321t1:c.935C>G
LRG_321:g.18958C>G
LRG_321p1:p.Thr312Ser
NC_000017.10:g.7576911G>C
NM_000546.4:c.935C>G
NM_000546.5(TP53):c.935C>G
NM_000546.5:c.935C>G
P04637:p.Thr312Ser
p.T312S

Protein change:

T153S

Links:

UniProtKB: P04637#VAR_045488; dbSNP: rs145151284

NCBI 1000 Genomes Browser:

rs145151284

Molecular consequence:

NM_000546.6:c.935C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.935C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.935C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.935C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.539C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.818C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.818C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.818C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.458C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.458C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.458C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.818C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.818C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000211763	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jan 18, 2018)	germline	clinical testing	Citation Link,
SCV001134881	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Oct 29, 2020)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 18511570, 12826609, 25886176, 19909015, 24278325, 30224644, 28861920, 27449771, 27619989, 26467025
SCV002011360	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000211763

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jan 18, 2018)

germline

clinical testing

Citation Link,

SCV001134881

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely benign
(Oct 29, 2020)

unknown

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV002011360

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 3, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families.

Bougeard G, Sesboüé R, Baert-Desurmont S, Vasseur S, Martin C, Tinat J, Brugières L, Chompret A, de Paillerets BB, Stoppa-Lyonnet D, Bonaïti-Pellié C, Frébourg T; French LFS working group.

J Med Genet. 2008 Aug;45(8):535-8. doi: 10.1136/jmg.2008.057570. Epub 2008 May 29.

PubMed [citation]

PMID:: 18511570

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]

PMID:: 12826609
PMCID:: PMC166245

See all PubMed Citations (11)

Details of each submission

From GeneDx, SCV000211763.14

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is denoted TP53 c.935C>G at the cDNA level, p.Thr312Ser (T312S) at the protein level, and results in the change of a Threonine to a Serine (ACC>AGC). This variant has been observed in at least one individual with a personal and/or family history suggestive of Li-Fraumeni syndrome (Bougeard 2008). Additionally, TP53 Thr312Ser has been identified in an individual with a head and neck cancer and in an individual with pancreatic cancer (Mafune 2015, Yang 2016). This variant is reported as having functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003). TP53 Thr312Ser was observed at an allele frequency of 0.029% (7/24028) in individuals of African ancestry in large population cohorts (Lek 2016). TP53 Thr312Ser is not located within a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether TP53 Thr312Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134881.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

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

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002011360.3

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

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

Last Updated: Nov 30, 2024

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