rs9840360
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000264731.8(TP63):c.1349+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,004 control chromosomes in the GnomAD database, including 36,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5115 hom., cov: 32)
Exomes 𝑓: 0.20 ( 31167 hom. )
Consequence
TP63
ENST00000264731.8 intron
ENST00000264731.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.66
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=-0.89).
BP6
Variant 3-189873036-G-A is Benign according to our data. Variant chr3-189873036-G-A is described in ClinVar as [Benign]. Clinvar id is 259126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189873036-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TP63 | NM_001114980.2 | c.1067+41G>A | intron_variant | ENST00000354600.10 | NP_001108452.1 | |||
TP63 | NM_003722.5 | c.1349+41G>A | intron_variant | ENST00000264731.8 | NP_003713.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TP63 | ENST00000264731.8 | c.1349+41G>A | intron_variant | 1 | NM_003722.5 | ENSP00000264731 | P4 | |||
TP63 | ENST00000354600.10 | c.1067+41G>A | intron_variant | 1 | NM_001114980.2 | ENSP00000346614 | A1 |
Frequencies
GnomAD3 genomes AF: 0.246 AC: 37391AN: 151796Hom.: 5111 Cov.: 32
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GnomAD3 exomes AF: 0.202 AC: 50518AN: 250562Hom.: 5619 AF XY: 0.204 AC XY: 27666AN XY: 135382
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GnomAD4 exome AF: 0.202 AC: 295645AN: 1461090Hom.: 31167 Cov.: 34 AF XY: 0.203 AC XY: 147836AN XY: 726900
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GnomAD4 genome AF: 0.246 AC: 37398AN: 151914Hom.: 5115 Cov.: 32 AF XY: 0.245 AC XY: 18167AN XY: 74242
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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 | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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