rs12489753
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_003722.5(TP63):c.579+3494C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0454 in 152,186 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.045 ( 208 hom., cov: 32)
Consequence
TP63
NM_003722.5 intron
NM_003722.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.103
Genes affected
TP63 (HGNC:15979): (tumor protein p63) This gene encodes a member of the p53 family of transcription factors. The functional domains of p53 family proteins include an N-terminal transactivation domain, a central DNA-binding domain and an oligomerization domain. Alternative splicing of this gene and the use of alternative promoters results in multiple transcript variants encoding different isoforms that vary in their functional properties. These isoforms function during skin development and maintenance, adult stem/progenitor cell regulation, heart development and premature aging. Some isoforms have been found to protect the germline by eliminating oocytes or testicular germ cells that have suffered DNA damage. Mutations in this gene are associated with ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3); split-hand/foot malformation 4 (SHFM4); ankyloblepharon-ectodermal defects-cleft lip/palate; ADULT syndrome (acro-dermato-ungual-lacrimal-tooth); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft 8. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP63 | NM_001114980.2 | c.297+3494C>T | intron_variant | ENST00000354600.10 | |||
TP63 | NM_003722.5 | c.579+3494C>T | intron_variant | ENST00000264731.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP63 | ENST00000264731.8 | c.579+3494C>T | intron_variant | 1 | NM_003722.5 | P4 | |||
TP63 | ENST00000354600.10 | c.297+3494C>T | intron_variant | 1 | NM_001114980.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0453 AC: 6891AN: 152068Hom.: 206 Cov.: 32
GnomAD3 genomes
?
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0454 AC: 6903AN: 152186Hom.: 208 Cov.: 32 AF XY: 0.0436 AC XY: 3242AN XY: 74410
GnomAD4 genome
?
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6903
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32
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3242
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165
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at