rs6789961
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003722.5(TP63):c.1130-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,607,668 control chromosomes in the GnomAD database, including 50,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.32 ( 9766 hom., cov: 32)
Exomes 𝑓: 0.23 ( 40341 hom. )
Consequence
TP63
NM_003722.5 intron
NM_003722.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.14
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 3-189869302-A-G is Benign according to our data. Variant chr3-189869302-A-G is described in ClinVar as [Benign]. Clinvar id is 259124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189869302-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP63 | NM_001114980.2 | c.848-22A>G | intron_variant | ENST00000354600.10 | |||
TP63 | NM_003722.5 | c.1130-22A>G | intron_variant | ENST00000264731.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP63 | ENST00000264731.8 | c.1130-22A>G | intron_variant | 1 | NM_003722.5 | P4 | |||
TP63 | ENST00000354600.10 | c.848-22A>G | intron_variant | 1 | NM_001114980.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.316 AC: 48059AN: 151942Hom.: 9745 Cov.: 32
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GnomAD3 exomes AF: 0.224 AC: 56225AN: 250938Hom.: 7671 AF XY: 0.221 AC XY: 29983AN XY: 135630
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GnomAD4 exome AF: 0.226 AC: 328802AN: 1455606Hom.: 40341 Cov.: 30 AF XY: 0.224 AC XY: 162432AN XY: 724606
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GnomAD4 genome ? AF: 0.316 AC: 48113AN: 152062Hom.: 9766 Cov.: 32 AF XY: 0.311 AC XY: 23098AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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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