3-189866712-G-C
Variant summary
Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_003722.5(TP63):c.797G>C(p.Arg266Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R266Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_003722.5 missense
Scores
Clinical Significance
Conservation
Publications
- ADULT syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
- ankyloblepharon-ectodermal defects-cleft lip/palate syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
- ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- limb-mammary syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
- Rapp-Hodgkin syndromeInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- premature ovarian failure 21Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- split hand-foot malformation 4Inheritance: AD Classification: MODERATE Submitted by: Illumina
- EEC syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- split hand-foot malformationInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TP63 | NM_003722.5 | c.797G>C | p.Arg266Pro | missense_variant | Exon 6 of 14 | ENST00000264731.8 | NP_003713.3 | |
TP63 | NM_001114980.2 | c.515G>C | p.Arg172Pro | missense_variant | Exon 4 of 12 | ENST00000354600.10 | NP_001108452.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TP63 | ENST00000264731.8 | c.797G>C | p.Arg266Pro | missense_variant | Exon 6 of 14 | 1 | NM_003722.5 | ENSP00000264731.3 | ||
TP63 | ENST00000354600.10 | c.515G>C | p.Arg172Pro | missense_variant | Exon 4 of 12 | 1 | NM_001114980.2 | ENSP00000346614.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Identified in a patient and her father both with TP63-related ectodermal dysplasia and oral clefting spectrum in published literature (PMID: 21204238); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as p.R237P; This variant is associated with the following publications: (PMID: 17224651, 21652629, 21204238, 32021595) -
Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at