VCV001767691.2 - ClinVar

NM_000546.6(TP53):c.965del (p.Pro322fs)

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.965del (p.Pro322fs)

Variation ID: 1767691 Accession: VCV001767691.2

Type and length

Deletion, 1 bp

Location

Cytogenetic: 17p13.1 17: 7673563 (GRCh38) [ NCBI UCSC ] 17: 7576881 (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	Nov 29, 2022	May 1, 2024	Oct 13, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000546.6:c.965del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000537.3:p.Pro322fs	frameshift
NM_001126112.3:c.965del	NP_001119584.1:p.Pro322fs	frameshift
NM_001126113.3:c.965del	NP_001119585.1:p.Pro322fs	frameshift
NM_001126114.3:c.965del	NP_001119586.1:p.Pro322fs	frameshift
NM_001126115.2:c.569del	NP_001119587.1:p.Pro190fs	frameshift
NM_001126116.2:c.569del	NP_001119588.1:p.Pro190fs	frameshift
NM_001126117.2:c.569del	NP_001119589.1:p.Pro190fs	frameshift
NM_001126118.2:c.848del	NP_001119590.1:p.Pro283fs	frameshift
NM_001276695.3:c.848del	NP_001263624.1:p.Pro283fs	frameshift
NM_001276696.3:c.848del	NP_001263625.1:p.Pro283fs	frameshift
NM_001276697.3:c.488del	NP_001263626.1:p.Pro163fs	frameshift
NM_001276698.3:c.488del	NP_001263627.1:p.Pro163fs	frameshift
NM_001276699.3:c.488del	NP_001263628.1:p.Pro163fs	frameshift
NM_001276760.3:c.848del	NP_001263689.1:p.Pro283fs	frameshift
NM_001276761.3:c.848del	NP_001263690.1:p.Pro283fs	frameshift
NM_001407262.1:c.964delC	NP_001394191.1:p.Pro322Hisfs	frameshift
NM_001407263.1:c.847delC	NP_001394192.1:p.Pro283Hisfs	frameshift
NM_001407264.1:c.964delC	NP_001394193.1:p.Pro322Hisfs	frameshift
NM_001407265.1:c.847delC	NP_001394194.1:p.Pro283Hisfs	frameshift
NM_001407266.1:c.964delC	NP_001394195.1:p.Pro322Hisfs	frameshift
NM_001407267.1:c.847delC	NP_001394196.1:p.Pro283Hisfs	frameshift
NM_001407268.1:c.964delC	NP_001394197.1:p.Pro322Hisfs	frameshift
NM_001407269.1:c.847delC	NP_001394198.1:p.Pro283Hisfs	frameshift
NM_001407270.1:c.964delC	NP_001394199.1:p.Pro322Hisfs	frameshift
NM_001407271.1:c.847delC	NP_001394200.1:p.Pro283Hisfs	frameshift
NR_176326.1:n.993delC
NC_000017.11:g.7673564del
NC_000017.10:g.7576882del
NG_017013.2:g.18988del
LRG_321:g.18988del
LRG_321t1:c.964del	LRG_321p1:p.Pro322Hisfs
LRG_321t2:c.964del	LRG_321:p.Pro322Hisfs
LRG_321t3:c.964del	LRG_321p3:p.Pro322Hisfs
LRG_321t4:c.964del	LRG_321p4:p.Pro322Hisfs
LRG_321t5:c.568del	LRG_321p5:p.Pro190Hisfs
LRG_321t6:c.568del	LRG_321p6:p.Pro190Hisfs
LRG_321t7:c.568del	LRG_321p7:p.Pro190Hisfs
LRG_321t8:c.847del	LRG_321p8:p.Pro283Hisfs

... more HGVS ... less HGVS

Protein change

P190fs, P163fs, P283fs, P322fs

Other names

Canonical SPDI

NC_000017.11:7673562:GG: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.
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Oct 13, 2022	RCV002385390.2

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 (Oct 13, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002694208.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: The c.965delC pathogenic mutation, located in coding exon 8 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 965, causing … (more) The c.965delC pathogenic mutation, located in coding exon 8 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 965, causing a translational frameshift with a predicted alternate stop codon (p.P322Hfs*23). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)

Comment:

The c.965delC pathogenic mutation, located in coding exon 8 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 965, causing a translational frameshift with a predicted alternate stop codon (p.P322Hfs*23). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated May 01, 2024

ClinVar Genomic variation as it relates to human health

NM_000546.6(TP53):c.965del (p.Pro322fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...