Variant 3-189886371-T-C 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.1350-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,611,378 control chromosomes in the GnomAD database, including 475,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42417 hom., cov: 32)

Exomes 𝑓: 0.77 ( 433380 hom. )

Consequence

TP63
NM_003722.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0850

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=-0.88).

BP6

Variant 3-189886371-T-C is Benign according to our data. Variant chr3-189886371-T-C is described in ClinVar as [Benign]. Clinvar id is 259127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189886371-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP63	NM_001114980.2 linkuse as main transcript	c.1068-23T>C		intron_variant		ENST00000354600.10
TP63	NM_003722.5 linkuse as main transcript	c.1350-23T>C		intron_variant		ENST00000264731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP63	ENST00000264731.8 linkuse as main transcript	c.1350-23T>C		intron_variant		1	NM_003722.5	P4	Q9H3D4-1
TP63	ENST00000354600.10 linkuse as main transcript	c.1068-23T>C		intron_variant		1	NM_001114980.2	A1	Q9H3D4-2

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113060

AN:

151954

Hom.:

42399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.748

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.605

Gnomad SAS

AF:

0.714

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.789

Gnomad OTH

AF:

0.764

GnomAD3 exomes

AF:

0.711

AC:

178228

AN:

250778

Hom.:

64804

AF XY:

0.723

AC XY:

97969

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.746

Gnomad AMR exome

AF:

0.501

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.598

Gnomad SAS exome

AF:

0.718

Gnomad FIN exome

AF:

0.696

Gnomad NFE exome

AF:

0.789

Gnomad OTH exome

AF:

0.737

GnomAD4 exome

AF:

0.768

AC:

1120877

AN:

1459304

Hom.:

433380

Cov.:

AF XY:

0.768

AC XY:

557986

AN XY:

726078

show subpopulations

Gnomad4 AFR exome

AF:

0.744

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.683

Gnomad4 EAS exome

AF:

0.635

Gnomad4 SAS exome

AF:

0.718

Gnomad4 FIN exome

AF:

0.703

Gnomad4 NFE exome

AF:

0.793

Gnomad4 OTH exome

AF:

0.762

GnomAD4 genome

AF:

0.744

AC:

113118

AN:

152074

Hom.:

42417

Cov.:

AF XY:

0.735

AC XY:

54599

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.748

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.692

Gnomad4 EAS

AF:

0.606

Gnomad4 SAS

AF:

0.714

Gnomad4 FIN

AF:

0.704

Gnomad4 NFE

AF:

0.789

Gnomad4 OTH

AF:

0.759

Alfa

AF:

0.716

Hom.:

7292

Bravo

AF:

0.736

Asia WGS

AF:

0.655

AC:

2283

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

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.6

DANN

Benign

0.67

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