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

Germline classification:: Benign (2 submissions)
Last evaluated:: Jun 14, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001260345.12

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:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001437278	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Sep 4, 2020)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 17606709, 21343334, 20407015, 26230955, 21519010, 27463065, 25952993, 22186996, 27680515, 27959731, 27895058, 22915647, 27276561 Citation Link,
SCV002065367	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jun 14, 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

SCV001437278

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Sep 4, 2020)

germline

clinical testing

PubMed (13)
[See all records that cite these PMIDs]

Citation Link,

SCV002065367

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Jun 14, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Transcriptional functionality of germ line p53 mutants influences cancer phenotype.

Monti P, Ciribilli Y, Jordan J, Menichini P, Umbach DM, Resnick MA, Luzzatto L, Inga A, Fronza G.

Clin Cancer Res. 2007 Jul 1;13(13):3789-95.

PubMed [citation]

PMID:: 17606709
PMCID:: PMC2128783

Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes.

Monti P, Perfumo C, Bisio A, Ciribilli Y, Menichini P, Russo D, Umbach DM, Resnick MA, Inga A, Fronza G.

Mol Cancer Res. 2011 Mar;9(3):271-9. doi: 10.1158/1541-7786.MCR-10-0496. Epub 2011 Feb 22.

PubMed [citation]

PMID:: 21343334
PMCID:: PMC3077904

See all PubMed Citations (14)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001437278.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

Variant summary: TP53 c.935C>G (p.Thr312Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.8e-05 in 251488 control chromosomes. The observed variant frequency is approximately 1.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Li-Fraumeni Syndrome phenotype (4e-05), suggesting that the variant is benign. At least one functional study showed this variant has transcriptional activity similar to wild-type (PHANTM database). Nine clinical diagnostic laboratories and one expert panel have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (bening/likely benign n=4, including the expert panel; VUS n=6). Based on the evidence outlined above, the variant was classified as benign.

#	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

From Genetic Services Laboratory, University of Chicago, SCV002065367.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 30, 2024

ClinVar

Relating variation to medicine