NM_000546.6(TP53):c.992A>G (p.Gln331Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 12, 2024
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:: RCV002289637.3

Allele description [Variation Report for NM_000546.6(TP53):c.992A>G (p.Gln331Arg)]

NM_000546.6(TP53):c.992A>G (p.Gln331Arg)

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.992A>G (p.Gln331Arg)

HGVS:

NC_000017.11:g.7673536T>C
NG_017013.2:g.19015A>G
NM_000546.6:c.992A>GMANE SELECT
NM_001126112.3:c.992A>G
NM_001126113.3:c.992A>G
NM_001126114.3:c.992A>G
NM_001126115.2:c.596A>G
NM_001126116.2:c.596A>G
NM_001126117.2:c.596A>G
NM_001126118.2:c.875A>G
NM_001276695.3:c.875A>G
NM_001276696.3:c.875A>G
NM_001276697.3:c.515A>G
NM_001276698.3:c.515A>G
NM_001276699.3:c.515A>G
NM_001276760.3:c.875A>G
NM_001276761.3:c.875A>G
NP_000537.3:p.Gln331Arg
NP_000537.3:p.Gln331Arg
NP_001119584.1:p.Gln331Arg
NP_001119585.1:p.Gln331Arg
NP_001119586.1:p.Gln331Arg
NP_001119587.1:p.Gln199Arg
NP_001119588.1:p.Gln199Arg
NP_001119589.1:p.Gln199Arg
NP_001119590.1:p.Gln292Arg
NP_001263624.1:p.Gln292Arg
NP_001263625.1:p.Gln292Arg
NP_001263626.1:p.Gln172Arg
NP_001263627.1:p.Gln172Arg
NP_001263628.1:p.Gln172Arg
NP_001263689.1:p.Gln292Arg
NP_001263690.1:p.Gln292Arg
LRG_321t1:c.992A>G
LRG_321:g.19015A>G
LRG_321p1:p.Gln331Arg
NC_000017.10:g.7576854T>C
NM_000546.4:c.992A>G
NM_000546.5:c.992A>G

Protein change:

Q172R

Links:

dbSNP: rs1064795056

NCBI 1000 Genomes Browser:

rs1064795056

Molecular consequence:

NM_000546.6:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.596A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.596A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.596A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.515A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.515A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.515A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.875A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002583227	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005036134	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Feb 12, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12826609, 16007150, 30224644 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002583227

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 18, 2022)

germline

clinical testing

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

SCV005036134

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Feb 12, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
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

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 (4)

Details of each submission

From Genome-Nilou Lab, SCV002583227.1

#	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

From Ambry Genetics, SCV005036134.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 23, 2024

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