NM_003722.5(TP63):c.62G>A (p.Arg21His) AND TP63-Related Spectrum Disorders

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 11, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002011531.4

Allele description [Variation Report for NM_003722.5(TP63):c.62G>A (p.Arg21His)]

NM_003722.5(TP63):c.62G>A (p.Arg21His)

Gene:

TP63:tumor protein p63 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q28

Genomic location:

Preferred name:

NM_003722.5(TP63):c.62G>A (p.Arg21His)

HGVS:

NC_000003.12:g.189631577G>A
NG_007550.3:g.39832G>A
NG_055551.1:g.974G>A
NM_001114978.2:c.62G>A
NM_001114979.2:c.62G>A
NM_001329144.2:c.62G>A
NM_001329148.2:c.62G>A
NM_001329964.2:c.56+34339G>A
NM_003722.5:c.62G>AMANE SELECT
NP_001108450.1:p.Arg21His
NP_001108451.1:p.Arg21His
NP_001316073.1:p.Arg21His
NP_001316077.1:p.Arg21His
NP_003713.3:p.Arg21His
LRG_428t1:c.62G>A
LRG_428:g.39832G>A
LRG_428p1:p.Arg21His
NC_000003.11:g.189349366G>A

Protein change:

R21H

Links:

dbSNP: rs766583971

NCBI 1000 Genomes Browser:

rs766583971

Molecular consequence:

NM_001329964.2:c.56+34339G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001114978.2:c.62G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114979.2:c.62G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329144.2:c.62G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329148.2:c.62G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003722.5:c.62G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: TP63-Related Spectrum Disorders
Identifiers:: MedGen: CN239305

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002303241	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002303241

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 11, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nothing to display

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002303241.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 21 of the TP63 protein (p.Arg21His). This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. This variant is present in population databases (rs766583971, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TP63-related conditions. ClinVar contains an entry for this variant (Variation ID: 1510128). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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