Variant chr3-189789729-C-CAGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001114980.2(TP63):c.-72_-71insAGAG variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.329 in 1,480,580 control chromosomes in the GnomAD database, including 81,348 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10440 hom., cov: 0)

Exomes 𝑓: 0.32 ( 70908 hom. )

Consequence

TP63
NM_001114980.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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:

TP63 (HGNC:):

TP63 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-189789729-C-CAGAG is Benign according to our data. Variant chr3-189789729-C-CAGAG is described in ClinVar as [Likely_benign]. Clinvar id is 802034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 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_-71insAGAG		5_prime_UTR_variant	1/12	ENST00000354600.10	NP_001108452.1	Q9H3D4-2
TP63	NM_003722.5 linkuse as main transcript	c.325-18543_325-18542insAGAG		intron_variant		ENST00000264731.8	NP_003713.3	Q9H3D4-1A0A0S2Z4N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000354600 linkuse as main transcript	c.-72_-71insAGAG		5_prime_UTR_variant	1/12	1	NM_001114980.2	ENSP00000346614.5		Q9H3D4-2
TP63	ENST00000264731.8 linkuse as main transcript	c.325-18543_325-18542insAGAG		intron_variant		1	NM_003722.5	ENSP00000264731.3		Q9H3D4-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54222

AN:

149706

Hom.:

10410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.552

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.342

GnomAD4 exome

AF:

0.325

AC:

432246

AN:

1330756

Hom.:

70908

Cov.:

AF XY:

0.323

AC XY:

212164

AN XY:

657698

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.544

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.363

AC:

54318

AN:

149824

Hom.:

10440

Cov.:

AF XY:

0.359

AC XY:

26240

AN XY:

73060

show subpopulations

Gnomad4 AFR

AF:

0.486

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.553

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.144

Hom.:

161

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

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