Variant rs6789961 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.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

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.14

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:

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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	Protein	UniProt
TP63	NM_001114980.2 linkuse as main transcript	c.848-22A>G		intron_variant		ENST00000354600.10	NP_001108452.1
TP63	NM_003722.5 linkuse as main transcript	c.1130-22A>G		intron_variant		ENST00000264731.8	NP_003713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8 linkuse as main transcript	c.1130-22A>G		intron_variant		1	NM_003722.5	ENSP00000264731	P4	Q9H3D4-1
TP63	ENST00000354600.10 linkuse as main transcript	c.848-22A>G		intron_variant		1	NM_001114980.2	ENSP00000346614	A1	Q9H3D4-2

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48059

AN:

151942

Hom.:

9745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.224

AC:

56225

AN:

250938

Hom.:

7671

AF XY:

0.221

AC XY:

29983

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.593

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.265

Gnomad EAS exome

AF:

0.156

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.219

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.226

AC:

328802

AN:

1455606

Hom.:

40341

Cov.:

AF XY:

0.224

AC XY:

162432

AN XY:

724606

show subpopulations

Gnomad4 AFR exome

AF:

0.600

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.316

AC:

48113

AN:

152062

Hom.:

9766

Cov.:

AF XY:

0.311

AC XY:

23098

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.583

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.241

Hom.:

7483

Bravo

AF:

0.330

Asia WGS

AF:

0.178

AC:

617

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

-0.61

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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