NM_000546.6(TP53):c.672G>A (p.Glu224=) AND Li-Fraumeni syndrome 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 10, 2024
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:: RCV002288559.3

Allele description [Variation Report for NM_000546.6(TP53):c.672G>A (p.Glu224=)]

NM_000546.6(TP53):c.672G>A (p.Glu224=)

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.672G>A (p.Glu224=)

HGVS:

NC_000017.11:g.7674859C>T
NG_017013.2:g.17692G>A
NM_000546.6:c.672G>AMANE SELECT
NM_001126112.3:c.672G>A
NM_001126113.3:c.672G>A
NM_001126114.3:c.672G>A
NM_001126115.1:c.276G>A
NM_001126115.2:c.276G>A
NM_001126116.1:c.276G>A
NM_001126116.2:c.276G>A
NM_001126117.1:c.276G>A
NM_001126117.2:c.276G>A
NM_001126118.2:c.555G>A
NM_001276695.3:c.555G>A
NM_001276696.3:c.555G>A
NM_001276697.3:c.195G>A
NM_001276698.3:c.195G>A
NM_001276699.3:c.195G>A
NM_001276760.3:c.555G>A
NM_001276761.3:c.555G>A
NP_000537.3:p.Glu224=
NP_000537.3:p.Glu224=
NP_001119584.1:p.Glu224=
NP_001119585.1:p.Glu224=
NP_001119586.1:p.Glu224=
NP_001119587.1:p.Glu92=
NP_001119588.1:p.Glu92=
NP_001119589.1:p.Glu92=
NP_001119590.1:p.Glu185=
NP_001263624.1:p.Glu185=
NP_001263625.1:p.Glu185=
NP_001263626.1:p.Glu65=
NP_001263627.1:p.Glu65=
NP_001263628.1:p.Glu65=
NP_001263689.1:p.Glu185=
NP_001263690.1:p.Glu185=
LRG_321t1:c.672G>A
LRG_321:g.17692G>A
LRG_321p1:p.Glu224=
NC_000017.10:g.7578177C>T
NC_000017.9:g.7518902C>T
NM_000546.4:c.672G>A
NM_000546.5:c.672G>A
NM_000546.6:c.672G>A

Links:

dbSNP: rs267605076

NCBI 1000 Genomes Browser:

rs267605076

Molecular consequence:

NM_000546.6:c.672G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126112.3:c.672G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126113.3:c.672G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126114.3:c.672G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126115.2:c.276G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126116.2:c.276G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126117.2:c.276G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126118.2:c.555G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276695.3:c.555G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276696.3:c.555G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276697.3:c.195G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276698.3:c.195G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276699.3:c.195G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276760.3:c.555G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276761.3:c.555G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

Condition(s)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

Recent activity

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Homo sapiens endogenous retrovirus group 48 member 1, envelope (ERVH48-1), mRNA
Homo sapiens endogenous retrovirus group 48 member 1, envelope (ERVH48-1), mRNA
gi|1929309599|ref|NM_001308491.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002583033	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004930373	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Jan 10, 2024)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28475293, 30709381 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002583033

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 18, 2022)

germline

clinical testing

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

SCV004930373

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Jan 10, 2024)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	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

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

Synonymous mutation in TP53 results in a cryptic splice site affecting its DNA-binding site in an adolescent with two primary sarcomas.

Austin F, Oyarbide U, Massey G, Grimes M, Corey SJ.

Pediatr Blood Cancer. 2017 Nov;64(11). doi: 10.1002/pbc.26584. Epub 2017 May 5.

PubMed [citation]

PMID:: 28475293
PMCID:: PMC5937697

See all PubMed Citations (3)

Details of each submission

From Genome-Nilou Lab, SCV002583033.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004930373.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is considered likely pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [PMID: 28475293]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 28475293, 30709381].

#	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: Sep 29, 2024

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