Variant 3-189789729-C-CAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001114980.2(TP63):c.-72_-71insAG variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0817 in 1,482,242 control chromosomes in the GnomAD database, including 5,607 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.070 ( 506 hom., cov: 0)

Exomes 𝑓: 0.083 ( 5101 hom. )

Consequence

TP63
NM_001114980.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.67

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 -10 ACMG points.

BP6

Variant 3-189789729-C-CAG is Benign according to our data. Variant chr3-189789729-C-CAG is described in ClinVar as [Benign]. Clinvar id is 1241414.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.122 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.-72_-71insAG		5_prime_UTR_variant	1/12	ENST00000354600.10	NP_001108452.1
TP63	NM_003722.5 linkuse as main transcript	c.325-18543_325-18542insAG		intron_variant		ENST00000264731.8	NP_003713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000354600.10 linkuse as main transcript	c.-72_-71insAG		5_prime_UTR_variant	1/12	1	NM_001114980.2	ENSP00000346614	A1	Q9H3D4-2
TP63	ENST00000264731.8 linkuse as main transcript	c.325-18543_325-18542insAG		intron_variant		1	NM_003722.5	ENSP00000264731	P4	Q9H3D4-1

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10456

AN:

149872

Hom.:

506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0111

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.0873

Gnomad EAS

AF:

0.00516

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.0929

Gnomad NFE

AF:

0.0836

Gnomad OTH

AF:

0.0794

GnomAD4 exome

AF:

0.0831

AC:

110704

AN:

1332252

Hom.:

5101

Cov.:

AF XY:

0.0835

AC XY:

54992

AN XY:

658412

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.0856

Gnomad4 EAS exome

AF:

0.00252

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.0820

Gnomad4 OTH exome

AF:

0.0792

GnomAD4 genome

AF:

0.0697

AC:

10460

AN:

149990

Hom.:

506

Cov.:

AF XY:

0.0725

AC XY:

5301

AN XY:

73150

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.0873

Gnomad4 EAS

AF:

0.00537

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.0836

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.0548

Hom.:

161

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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