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NM_000546.6(TP53):c.313G>A (p.Gly105Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jun 18, 2022
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:
RCV000492331.3

Allele description [Variation Report for NM_000546.6(TP53):c.313G>A (p.Gly105Ser)]

NM_000546.6(TP53):c.313G>A (p.Gly105Ser)

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.313G>A (p.Gly105Ser)
HGVS:
  • NC_000017.11:g.7676056C>T
  • NG_017013.2:g.16495G>A
  • NM_000546.6:c.313G>AMANE SELECT
  • NM_001126112.3:c.313G>A
  • NM_001126113.3:c.313G>A
  • NM_001126114.3:c.313G>A
  • NM_001126118.2:c.196G>A
  • NM_001276695.3:c.196G>A
  • NM_001276696.3:c.196G>A
  • NM_001276760.3:c.196G>A
  • NM_001276761.3:c.196G>A
  • NP_000537.3:p.Gly105Ser
  • NP_001119584.1:p.Gly105Ser
  • NP_001119585.1:p.Gly105Ser
  • NP_001119586.1:p.Gly105Ser
  • NP_001119590.1:p.Gly66Ser
  • NP_001263624.1:p.Gly66Ser
  • NP_001263625.1:p.Gly66Ser
  • NP_001263689.1:p.Gly66Ser
  • NP_001263690.1:p.Gly66Ser
  • LRG_321:g.16495G>A
  • NC_000017.10:g.7579374C>T
  • NM_000546.4:c.313G>A
  • NM_001276760.2:c.196G>A
Protein change:
G105S
Links:
dbSNP: rs1060501195
Molecular consequence:
  • NM_000546.6:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000581123Ambry Genetics
criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))		Likely pathogenic
(Mar 17, 2016) 		germlineclinical testing

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

Citation Link,

SCV002582410Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jun 18, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin.

Bendig I, Mohr N, Kramer F, Weber BH.

Cancer Genet Cytogenet. 2004 Oct 1;154(1):22-6.

PubMed [citation]
PMID:
15381368

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 Ambry Genetics, SCV000581123.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

<span style="font-size:12px">The p.G105S variant (also known as c.313G>A), located in coding exon 3 of the TP53 gene, results from a G to A substitution at nucleotide position 313. The glycine at codon 105 is replaced by serine, an amino acid with similar properties.<span style="font-family:arial,sans-serif">This alteration is located in the functionally critical DNA binding domain and has shown a loss of transactivation activity in yeast based functional studies (Kato S et al. <span style="font-family:arial,sans-serif">Proc<span style="font-family:arial,sans-serif"> <span style="font-family:arial,sans-serif">Natl<span style="font-family:arial,sans-serif"> <span style="font-family:arial,sans-serif">Acad<span style="font-family:arial,sans-serif"> <span style="font-family:arial,sans-serif">Sci USA<span style="font-family:arial,sans-serif">. 2003 Jul 8;100(14):8424-9). Although this specific alteration has not been reported in the literature, another alteration at this position (p.G105C) was reported in a family with classic Li-Fraumeni Syndrome, where the proband had three primary breast cancers by the age of 31, and a family history of early onset breast cancer and brain tumors (Bendig I et al., <span style="font-family:arial,sans-serif">Cancer Genet. <span style="font-family:arial,sans-serif">Cytogenet<span style="font-family:arial,sans-serif">.<span style="font-family:arial,sans-serif"> <span style="font-family:arial,sans-serif">2004 Oct; 154(1):22-6). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Cho Y et al., <span style="font-family:arial,sans-serif">Science 1994 Jul; 265(5170):346-55). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT <span style="font-family:arial,sans-serif">in silico<span style="font-family:arial,sans-serif"> analyses, respectively. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Genome-Nilou Lab, SCV002582410.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 12, 2026

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