Variant rs34875865 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.191+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,613,296 control chromosomes in the GnomAD database, including 2,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 197 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2347 hom. )

Consequence

TP63
NM_003722.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.761

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=-0.84).

BP6

Variant 3-189737892-T-C is Benign according to our data. Variant chr3-189737892-T-C is described in ClinVar as [Benign]. Clinvar id is 259131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189737892-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.058 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.191+24T>C		intron_variant		ENST00000264731.8	NP_003713.3	Q9H3D4-1A0A0S2Z4N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8 linkuse as main transcript	c.191+24T>C		intron_variant		1	NM_003722.5	ENSP00000264731.3		Q9H3D4-1

Frequencies

GnomAD3 genomes

AF:

0.0354

AC:

5391

AN:

152100

Hom.:

197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00789

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0595

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0379

AC:

9475

AN:

250330

Hom.:

312

AF XY:

0.0377

AC XY:

5096

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.00727

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0553

Gnomad NFE exome

AF:

0.0611

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0510

AC:

74549

AN:

1461078

Hom.:

2347

Cov.:

AF XY:

0.0501

AC XY:

36421

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.00774

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.00452

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.0571

Gnomad4 NFE exome

AF:

0.0598

Gnomad4 OTH exome

AF:

0.0401

GnomAD4 genome

AF:

0.0354

AC:

5392

AN:

152218

Hom.:

197

Cov.:

AF XY:

0.0339

AC XY:

2526

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00787

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.0557

Gnomad4 NFE

AF:

0.0595

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0486

Hom.:

Bravo

AF:

0.0317

Asia WGS

AF:

0.00808

AC:

AN:

3478

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.9

DANN

Benign

0.73

Splicing

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