NM_000546.6(TP53):c.991C>T (p.Gln331Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 27, 2023
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:: RCV001183200.5

Allele description [Variation Report for NM_000546.6(TP53):c.991C>T (p.Gln331Ter)]

NM_000546.6(TP53):c.991C>T (p.Gln331Ter)

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.991C>T (p.Gln331Ter)

HGVS:

NC_000017.11:g.7673537G>A
NG_017013.2:g.19014C>T
NM_000546.4:c.991C>T
NM_000546.6:c.991C>TMANE SELECT
NM_001126112.3:c.991C>T
NM_001126113.3:c.991C>T
NM_001126114.3:c.991C>T
NM_001126115.2:c.595C>T
NM_001126116.2:c.595C>T
NM_001126117.2:c.595C>T
NM_001126118.2:c.874C>T
NM_001276695.3:c.874C>T
NM_001276696.3:c.874C>T
NM_001276697.3:c.514C>T
NM_001276698.3:c.514C>T
NM_001276699.3:c.514C>T
NM_001276760.3:c.874C>T
NM_001276761.3:c.874C>T
NP_000537.3:p.Gln331Ter
NP_001119584.1:p.Gln331Ter
NP_001119585.1:p.Gln331Ter
NP_001119586.1:p.Gln331Ter
NP_001119587.1:p.Gln199Ter
NP_001119588.1:p.Gln199Ter
NP_001119589.1:p.Gln199Ter
NP_001119590.1:p.Gln292Ter
NP_001263624.1:p.Gln292Ter
NP_001263625.1:p.Gln292Ter
NP_001263626.1:p.Gln172Ter
NP_001263627.1:p.Gln172Ter
NP_001263628.1:p.Gln172Ter
NP_001263689.1:p.Gln292Ter
NP_001263690.1:p.Gln292Ter
LRG_321t1:c.991C>T
LRG_321:g.19014C>T
NC_000017.10:g.7576855G>A
NC_000017.10:g.7576855G>A
NM_000546.5:c.991C>T
NM_000546.6:c.991C>T

Protein change:

Q172*

Links:

dbSNP: rs1597359130

NCBI 1000 Genomes Browser:

rs1597359130

Molecular consequence:

NM_000546.6:c.991C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126112.3:c.991C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126113.3:c.991C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126114.3:c.991C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126115.2:c.595C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126116.2:c.595C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126117.2:c.595C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126118.2:c.874C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276695.3:c.874C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276696.3:c.874C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276697.3:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276698.3:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276699.3:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276760.3:c.874C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276761.3:c.874C>T - nonsense - [Sequence Ontology: SO:0001587]

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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LOC115159220 [Salmo trutta]
LOC115159220 [Salmo trutta]
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001348858	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 2, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003995353	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 27, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001348858

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 2, 2020)

germline

clinical testing

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

SCV003995353

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 27, 2023)

germline

clinical testing

Citation Link

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 Color Diagnostics, LLC DBA Color Health, SCV001348858.2

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

Description

This variant is located in the TP53 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	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 Ambry Genetics, SCV003995353.2

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

Description

The p.Q331* pathogenic mutation (also known as c.991C>T), located in coding exon 8 of the TP53 gene, results from a C to T substitution at nucleotide position 991. This changes the amino acid from a glutamine to a stop codon within coding exon 8. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: Oct 8, 2024

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