NM_000546.6(TP53):c.375G>A (p.Thr125=) AND TP53-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 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:: RCV003398806.4

Allele description [Variation Report for NM_000546.6(TP53):c.375G>A (p.Thr125=)]

NM_000546.6(TP53):c.375G>A (p.Thr125=)

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.375G>A (p.Thr125=)

HGVS:

NC_000017.11:g.7675994C>T
NG_017013.2:g.16557G>A
NM_000546.6:c.375G>AMANE SELECT
NM_001126112.3:c.375G>A
NM_001126113.3:c.375G>A
NM_001126114.3:c.375G>A
NM_001126118.2:c.258G>A
NM_001276695.3:c.258G>A
NM_001276696.3:c.258G>A
NM_001276760.3:c.258G>A
NM_001276761.3:c.258G>A
NP_000537.3:p.Thr125=
NP_000537.3:p.Thr125=
NP_001119584.1:p.Thr125=
NP_001119585.1:p.Thr125=
NP_001119586.1:p.Thr125=
NP_001119590.1:p.Thr86=
NP_001263624.1:p.Thr86=
NP_001263625.1:p.Thr86=
NP_001263689.1:p.Thr86=
NP_001263690.1:p.Thr86=
LRG_321t1:c.375G>A
LRG_321:g.16557G>A
LRG_321p1:p.Thr125=
NC_000017.10:g.7579312C>T
NM_000546.4:c.375G>A
NM_000546.5:c.375G>A
p.Thr125Thr

Links:

dbSNP: rs55863639

NCBI 1000 Genomes Browser:

rs55863639

Molecular consequence:

NM_000546.6:c.375G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126112.3:c.375G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126113.3:c.375G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126114.3:c.375G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126118.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276695.3:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276696.3:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276760.3:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276761.3:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

Condition(s)

Name:: TP53-related disorder
Synonyms:: TP53-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004111187	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 19, 2022)	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

SCV004111187

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 19, 2022)

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004111187.1

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

Description

The TP53 c.375G>A variant is not predicted to result in an amino acid change (p.=). This variant is predicted to strongly reduce the stregth of the neighboring splice donor site. This variant has been reported in several individuals with Li-Fraumeni and Li-Fraumeni-like syndrome (see for example, Warneford et al 1992. PubMed ID: 1467311; Wasserman JD et al 2015. PubMed ID: 25584008). These studies and others provide evidence that this variant segregates with disease in families and disrupts TP53 splicing. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is classified as pathogenic by several laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/177825/). We also clasify this variant as patogenic.

#	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

Last Updated: Jun 17, 2024

ClinVar

Relating variation to medicine