Variant rs2276792 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003722.5(TP63):c.766+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,577,000 control chromosomes in the GnomAD database, including 14,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3974 hom., cov: 30)

Exomes 𝑓: 0.11 ( 10318 hom. )

Consequence

TP63
NM_003722.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.36

Variant links:

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]

TP63 links:

TP63 (HGNC:):

TP63 links:

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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=-0.83).

BP6

Variant 3-189864460-G-A is Benign according to our data. Variant chr3-189864460-G-A is described in ClinVar as [Benign]. Clinvar id is 259133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189864460-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP63	NM_003722.5 linkuse as main transcript	c.766+42G>A		intron_variant		ENST00000264731.8	NP_003713.3	Q9H3D4-1A0A0S2Z4N5
TP63	NM_001114980.2 linkuse as main transcript	c.484+42G>A		intron_variant		ENST00000354600.10	NP_001108452.1	Q9H3D4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8 linkuse as main transcript	c.766+42G>A		intron_variant		1	NM_003722.5	ENSP00000264731.3		Q9H3D4-1
TP63	ENST00000354600.10 linkuse as main transcript	c.484+42G>A		intron_variant		1	NM_001114980.2	ENSP00000346614.5		Q9H3D4-2

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

27945

AN:

151040

Hom.:

3967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.0930

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.124

AC:

27684

AN:

223324

Hom.:

2474

AF XY:

0.121

AC XY:

14611

AN XY:

120458

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.0676

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.160

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0956

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.108

AC:

154460

AN:

1425852

Hom.:

10318

Cov.:

AF XY:

0.108

AC XY:

76572

AN XY:

706178

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.0743

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0955

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.185

AC:

27963

AN:

151148

Hom.:

3974

Cov.:

AF XY:

0.183

AC XY:

13477

AN XY:

73810

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.0930

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.124

Hom.:

965

Bravo

AF:

0.196

Asia WGS

AF:

0.145

AC:

505

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.11

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over