NM_000546.5(TP53):c.354A>T (p.Thr118=) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Jul 2, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000421071.3

Allele description [Variation Report for NM_000546.5(TP53):c.354A>T (p.Thr118=)]

NM_000546.5(TP53):c.354A>T (p.Thr118=)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.354A>T (p.Thr118=)
HGVS:
  • NC_000017.11:g.7676015T>A
  • NG_017013.2:g.16536A>T
  • NM_000546.5:c.354A>T
  • NM_001126112.2:c.354A>T
  • NM_001126113.2:c.354A>T
  • NM_001126114.2:c.354A>T
  • NM_001126118.1:c.237A>T
  • NM_001276695.2:c.237A>T
  • NM_001276696.2:c.237A>T
  • NM_001276760.2:c.237A>T
  • NM_001276761.2:c.237A>T
  • NP_000537.3:p.Thr118=
  • NP_001119584.1:p.Thr118=
  • NP_001119585.1:p.Thr118=
  • NP_001119586.1:p.Thr118=
  • NP_001119590.1:p.Thr79=
  • NP_001263624.1:p.Thr79=
  • NP_001263625.1:p.Thr79=
  • NP_001263689.1:p.Thr79=
  • NP_001263690.1:p.Thr79=
  • LRG_321t1:c.354A>T
  • LRG_321t2:c.354A>T
  • LRG_321t3:c.354A>T
  • LRG_321t4:c.354A>T
  • LRG_321t8:c.237A>T
  • LRG_321:g.16536A>T
  • LRG_321:p.Thr118=
  • LRG_321p1:p.Thr118=
  • LRG_321p3:p.Thr118=
  • LRG_321p4:p.Thr118=
  • LRG_321p8:p.Thr79=
  • NC_000017.10:g.7579333T>A
  • NM_000546.4:c.354A>T
  • p.T118T
  • p.Thr118Thr
Links:
dbSNP: rs751978853
NCBI 1000 Genomes Browser:
rs751978853
Molecular consequence:
  • NM_000546.5:c.354A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126112.2:c.354A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126113.2:c.354A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126114.2:c.354A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126118.1:c.237A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276695.2:c.237A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276696.2:c.237A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276760.2:c.237A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276761.2:c.237A>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000514936GeneDxcriteria provided, single submitter
Benign
(Jul 16, 2015)
germlineclinical testing

Citation Link,

SCV000602267Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Likely benign
(Jan 19, 2017)
germlineclinical testing

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

SCV000920319Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Jul 2, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000514936.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000602267.1

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920319.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: TP53 c.354A>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.7e-05 in 245848 control chromosomes (gnomAD). The observed variant frequency is approximately 1.43 folds higher than the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Li-Fraumeni Syndrome phenotype (4e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.354A>T in individuals affected with Li-Fraumeni Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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