VCV000006536.1 - ClinVar

NM_003722.5(TP63):c.1681T>G (p.Cys561Gly)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003722.5(TP63):c.1681T>G (p.Cys561Gly)

Variation ID: 6536 Accession: VCV000006536.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q28 3: 189890817 (GRCh38) [ NCBI UCSC ] 3: 189608606 (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	Jan 8, 2018	Jan 8, 2018	Feb 1, 2001

HGVS

Nucleotide	Protein	Molecular consequence
NM_001114978.2:c.1652+1333T>G		intron variant
NM_001114980.2:c.1399T>G	NP_001108452.1:p.Cys467Gly	missense
NM_001114981.2:c.1370+1333T>G		intron variant
NM_001329144.2:c.1508-3389T>G		intron variant
NM_001329145.2:c.1226-3389T>G		intron variant
NM_001329146.2:c.1144T>G	NP_001316075.1:p.Cys382Gly	missense
NM_001329148.2:c.1669T>G	NP_001316077.1:p.Cys557Gly	missense
NM_001329149.2:c.1214-3389T>G		intron variant
NM_001329150.2:c.959-3389T>G		intron variant
NM_001329964.1:c.1675T>G	NP_001316893.1:p.Cys559Gly	missense
NM_003722.5:c.1681T>G	NP_003713.3:p.Cys561Gly	missense
NC_000003.12:g.189890817T>G
NC_000003.11:g.189608606T>G
NG_007550.1:g.264391T>G
NG_007550.2:g.264391T>G
NG_007550.3:g.299072T>G
	Q9H3D4:p.Cys561Gly

... more HGVS ... less HGVS

Protein change

C561G, C467G, C382G, C557G, C559G

Other names

TP63, CYS522GLY

Canonical SPDI

NC_000003.12:189890816:T:G

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

ClinGen: CA253875 UniProtKB: Q9H3D4#VAR_020881 OMIM: 603273.0010 dbSNP: rs121908843 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 11159940 to determine the location of this allele on current reference sequence.

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.
TP63		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	822	886

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.
Hay-Wells syndrome of ectodermal dysplasia	Pathogenic (1)	no assertion criteria provided	Feb 1, 2001	RCV000006910.3

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.	Expand all rows Collapse all rows 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 (Feb 01, 2001)	no assertion criteria provided	ANKYLOBLEPHARON-ECTODERMAL DEFECTS-CLEFT LIP/PALATE	OMIM Accession: SCV000027106.2 First in ClinVar: Apr 04, 2013 Last updated: Jan 08, 2018	Publications: PubMed (2) PubMed: 11159940‚ 9774969 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In a 10-month-old infant with typical features of Hay-Wells syndrome (AEC; 106260), McGrath et al. (2001) identified a T-to-G transversion at nucleotide 1564 of the … (more) In a 10-month-old infant with typical features of Hay-Wells syndrome (AEC; 106260), McGrath et al. (2001) identified a T-to-G transversion at nucleotide 1564 of the TP63 gene, resulting in a cys526-to-gly substitution in the sterile alpha motif (SAM) domain. Molecular modeling suggested that the substitution would alter protein-protein interactions. According the sequence reported by Yang et al. (1998), this mutation is designated cys522 to gly. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.	McGrath JA	Human molecular genetics	2001	PMID: 11159940
p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.	Yang A	Molecular cell	1998	PMID: 9774969

Text-mined citations for rs121908843 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 10, 2021