NM_000546.6(TP53):c.480G>A (p.Met160Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 11, 2025
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:: RCV000218200.13

Allele description [Variation Report for NM_000546.6(TP53):c.480G>A (p.Met160Ile)]

NM_000546.6(TP53):c.480G>A (p.Met160Ile)

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.480G>A (p.Met160Ile)

Other names:

NM_000546.5(TP53):c.480G>A

HGVS:

NC_000017.11:g.7675132C>T
NG_017013.2:g.17419G>A
NM_000546.6:c.480G>AMANE SELECT
NM_001126112.3:c.480G>A
NM_001126113.3:c.480G>A
NM_001126114.3:c.480G>A
NM_001126115.2:c.84G>A
NM_001126116.2:c.84G>A
NM_001126117.2:c.84G>A
NM_001126118.2:c.363G>A
NM_001276695.3:c.363G>A
NM_001276696.3:c.363G>A
NM_001276697.3:c.3G>A
NM_001276698.3:c.3G>A
NM_001276699.3:c.3G>A
NM_001276760.3:c.363G>A
NM_001276761.3:c.363G>A
NP_000537.3:p.Met160Ile
NP_000537.3:p.Met160Ile
NP_001119584.1:p.Met160Ile
NP_001119585.1:p.Met160Ile
NP_001119586.1:p.Met160Ile
NP_001119587.1:p.Met28Ile
NP_001119588.1:p.Met28Ile
NP_001119589.1:p.Met28Ile
NP_001119590.1:p.Met121Ile
NP_001263624.1:p.Met121Ile
NP_001263625.1:p.Met121Ile
NP_001263626.1:p.Met1Ile
NP_001263627.1:p.Met1Ile
NP_001263628.1:p.Met1Ile
NP_001263689.1:p.Met121Ile
NP_001263690.1:p.Met121Ile
LRG_321t1:c.480G>A
LRG_321:g.17419G>A
LRG_321p1:p.Met160Ile
NC_000017.10:g.7578450C>T
NM_000546.4:c.480G>A
NM_000546.5:c.480G>A
P04637:p.Met160Ile

Protein change:

M121I

Links:

UniProtKB: P04637#VAR_005908; dbSNP: rs772354334

Molecular consequence:

NM_001276697.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001276698.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001276699.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000546.6:c.480G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.480G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.480G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.480G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.84G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.84G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.84G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.363G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.363G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.363G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.363G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.363G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; 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
SCV000274415	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 2, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29785153, 30224644, 31159747 Citation Link,
SCV000686742	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 11, 2025)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1282660, 29785153, 29979965, 30224644, 25741868
SCV000822207	GeneKor MSA	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 1, 2018)	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

SCV000274415

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 2, 2023)

germline

clinical testing

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

Citation Link,

SCV000686742

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 11, 2025)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV000822207

GeneKor MSA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 1, 2018)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]

PMID:: 31159747
PMCID:: PMC6547505

Signal transduction via the fibronectin receptor: do integrins regulate matrix remodeling?

Damsky C, Tremble P, Werb Z.

Matrix Suppl. 1992;1:184-91.

PubMed [citation]

PMID:: 1282660

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV000274415.8

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

Description

The p.M160I variant (also known as c.480G>A), located in coding exon 4 of the TP53 gene, results from a G to A substitution at nucleotide position 480. The methionine at codon 160 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in cohorts undergoing evaluation for inherited cancer predisposition (Goidescu IG et al. Clujul Med, 2018 Apr;91:157-165; Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This variant is in the DNA binding domain of the TP53 protein and is reported to have partially functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has no dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000686742.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This missense variant replaces methionine with isoleucine at codon 160 of the TP53 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. Functional studies have shown this variant to have neutral effect on TP53 protein function (PMID: 1282660, 29979965, 30224644). This variant has been reported in an individual affected with breast cancer (PMID 29785153). This variant has been identified in 3/251310 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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 GeneKor MSA, SCV000822207.2

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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