VCV002033884.2 - ClinVar

NM_000546.6(TP53):c.372del (p.Thr123_Cys124insTer)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000546.6(TP53):c.372del (p.Thr123_Cys124insTer)

Variation ID: 2033884 Accession: VCV002033884.2

Type and length

Deletion, 1 bp

Location

Cytogenetic: 17p13.1 17: 7675997 (GRCh38) [ NCBI UCSC ] 17: 7579315 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 8, 2023	Feb 20, 2024	Nov 29, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000546.6:c.372del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000537.3:p.Thr123_Cys124insTer	nonsense
NM_001126112.3:c.372del	NP_001119584.1:p.Thr123_Cys124insTer	nonsense
NM_001126113.3:c.372del	NP_001119585.1:p.Thr123_Cys124insTer	nonsense
NM_001126114.3:c.372del	NP_001119586.1:p.Thr123_Cys124insTer	nonsense
NM_001126118.2:c.255del	NP_001119590.1:p.Thr84_Cys85insTer	nonsense
NM_001276695.3:c.255del	NP_001263624.1:p.Thr84_Cys85insTer	nonsense
NM_001276696.3:c.255del	NP_001263625.1:p.Thr84_Cys85insTer	nonsense
NM_001276760.3:c.255del	NP_001263689.1:p.Thr84_Cys85insTer	nonsense
NM_001276761.3:c.255del	NP_001263690.1:p.Thr84_Cys85insTer	nonsense
NM_001407262.1:c.372delC	NP_001394191.1:p.Cys124Terfs	frameshift nonsense
NM_001407263.1:c.255delC	NP_001394192.1:p.Cys85Terfs	frameshift nonsense
NM_001407264.1:c.372delC	NP_001394193.1:p.Cys124Terfs	frameshift nonsense
NM_001407265.1:c.255delC	NP_001394194.1:p.Cys85Terfs	frameshift nonsense
NM_001407266.1:c.372delC	NP_001394195.1:p.Cys124Terfs	frameshift nonsense
NM_001407267.1:c.255delC	NP_001394196.1:p.Cys85Terfs	frameshift nonsense
NM_001407268.1:c.372delC	NP_001394197.1:p.Cys124Terfs	frameshift nonsense
NM_001407269.1:c.255delC	NP_001394198.1:p.Cys85Terfs	frameshift nonsense
NM_001407270.1:c.372delC	NP_001394199.1:p.Cys124Terfs	frameshift nonsense
NM_001407271.1:c.255delC	NP_001394200.1:p.Cys85Terfs	frameshift nonsense
NR_176326.1:n.514delC
NC_000017.11:g.7675997del
NC_000017.10:g.7579315del
NG_017013.2:g.16554del
LRG_321:g.16554del
LRG_321t1:c.372del	LRG_321p1:p.Cys124Terfs
LRG_321t2:c.372del	LRG_321:p.Cys124Terfs
LRG_321t3:c.372del	LRG_321p3:p.Cys124Terfs
LRG_321t4:c.372del	LRG_321p4:p.Cys124Terfs
LRG_321t8:c.255del	LRG_321p8:p.Cys85Terfs

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:7675996:G:

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TP53		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3367	3466

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Li-Fraumeni syndrome	Pathogenic (1)	criteria provided, single submitter	Nov 29, 2022	RCV002872712.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Nov 29, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Li-Fraumeni syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003238038.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024	Publications: PubMed (2) PubMed: 20522432‚ 32658383 Comment: This sequence change creates a premature translational stop signal (p.Cys124) in the TP53 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Cys124) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with rhabdomyosarcoma (PMID: 32658383). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). (less)

Comment:

This sequence change creates a premature translational stop signal (p.Cys124*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with rhabdomyosarcoma (PMID: 32658383). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Rhabdomyosarcoma associated with germline TP53 alteration in children and adolescents: The French experience.	Pondrom M	Pediatric blood & cancer	2020	PMID: 32658383
TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.	Ruijs MW	Journal of medical genetics	2010	PMID: 20522432

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000546.6(TP53):c.372del (p.Thr123_Cys124insTer)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...