NM_000546.6(TP53):c.91G>A (p.Val31Ile) AND not provided

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Sep 16, 2020
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:: RCV000586196.13

Allele description [Variation Report for NM_000546.6(TP53):c.91G>A (p.Val31Ile)]

NM_000546.6(TP53):c.91G>A (p.Val31Ile)

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.91G>A (p.Val31Ile)

Other names:

p.V31I:GTT>ATT

HGVS:

NC_000017.11:g.7676387C>T
NG_017013.2:g.16164G>A
NM_000546.6:c.91G>AMANE SELECT
NM_001126112.3:c.91G>A
NM_001126113.3:c.91G>A
NM_001126114.3:c.91G>A
NM_001126118.2:c.-27G>A
NM_001276695.3:c.-27G>A
NM_001276696.3:c.-27G>A
NM_001276760.3:c.-27G>A
NM_001276761.3:c.-27G>A
NP_000537.3:p.Val31Ile
NP_000537.3:p.Val31Ile
NP_001119584.1:p.Val31Ile
NP_001119585.1:p.Val31Ile
NP_001119586.1:p.Val31Ile
LRG_321t1:c.91G>A
LRG_321:g.16164G>A
LRG_321p1:p.Val31Ile
NC_000017.10:g.7579705C>T
NM_000546.4:c.91G>A
NM_000546.5:c.91G>A
P04637:p.Val31Ile
p.V31I

Protein change:

V31I

Links:

UniProtKB: P04637#VAR_044554; dbSNP: rs201753350

NCBI 1000 Genomes Browser:

rs201753350

Molecular consequence:

NM_001126118.2:c.-27G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-27G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-27G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-27G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-27G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.91G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000697455	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17690113, 27374712, 20436704, 26332594, 1565143, 24728327 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV002046225	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Sep 16, 2020)	unknown	clinical testing	PubMed (17) [See all records that cite these PMIDs] 17690113, 12826609, 14559903, 30287823, 31016814, 30352134, 27374712, 26230955, 30840781, 26332594, 25856671, 25186627, 24896186, 23555315, 20436704, 1565143, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000697455

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV002046225

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely benign
(Sep 16, 2020)

unknown

clinical testing

PubMed (17)
[See all records that cite these PMIDs]

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

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

Identification and characterization of a novel germ line p53 mutation in familial gastric cancer in the Japanese population.

Yamada H, Shinmura K, Okudela K, Goto M, Suzuki M, Kuriki K, Tsuneyoshi T, Sugimura H.

Carcinogenesis. 2007 Sep;28(9):2013-8. Epub 2007 Aug 8.

PubMed [citation]

PMID:: 17690113

See all PubMed Citations (18)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697455.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: The c.91G>A (p.Val31Ile) in TP53 gene is a missense change that involves a conserved nucleotide. The variant is located just outside of the p53 transactivation domain. Although 4/5 in silico tools predict benign outcome, in the functional studies the variant displayed moderately reduced cell proliferation suppressing activity as well as transcriptional activity on p21 (CDKN1A) and MDM2 promoters, but not on the BAX promoter compared to wt-tp53 (Yamada, 2007). In addition, it is also classified as functionally competent variant in TP53 database. The variant is present in the large control population dataset of ExAC and gnomAD at a similar frequencies of 0.00026 (31/118406 and 58/275552 chromosomes tested, respectively), predominantly in individuals of East Asian descent (0.00353; 30/ 8498 chromosomes and 58/18782 chromosomes tested) including one homozygote. These frequencies exceed the maximal expected frequency of a pathogenic allele (0.000047) in this gene. The variant has been reported in several cancer-affected individuals without evidence for causality (Toguchida, 1992; Lee, 2010; Yamada, 2007; Yamaguchi, 2016) and is generally regarded as a polymorphism. In addition, one individual dx with thyroid carcinoma tested positive for BRAF V600E, further supporting benign outcome of the variant of interest. The variant was also identified in one internal LCA specimen in co-occurrence with a known pathogenic variant in MSH6 c.4068_4071dupGATT (p.K1358fs*2). Lastly, multiple reputable databases/clinical laboratories cite the variant with classification of Likely Benign. Taking all lines of evidence into consideration, this variant has been classified as Benign.

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002046225.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (17)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine