Variant 3-189868841-C-G 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 ENST00000264731.8(TP63):c.1129+125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,482,662 control chromosomes in the GnomAD database, including 19,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1507 hom., cov: 32)

Exomes 𝑓: 0.16 ( 17643 hom. )

Consequence

TP63
ENST00000264731.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.294

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=-0.86).

BP6

Variant 3-189868841-C-G is Benign according to our data. Variant chr3-189868841-C-G is described in ClinVar as [Benign]. Clinvar id is 1238951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 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.847+125C>G		intron_variant		ENST00000354600.10	NP_001108452.1
TP63	NM_003722.5 linkuse as main transcript	c.1129+125C>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.1129+125C>G		intron_variant		1	NM_003722.5	ENSP00000264731	P4	Q9H3D4-1
TP63	ENST00000354600.10 linkuse as main transcript	c.847+125C>G		intron_variant		1	NM_001114980.2	ENSP00000346614	A1	Q9H3D4-2

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19164

AN:

152006

Hom.:

1508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.0562

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.122

GnomAD4 exome

AF:

0.159

AC:

211559

AN:

1330536

Hom.:

17643

AF XY:

0.162

AC XY:

108377

AN XY:

668632

show subpopulations

Gnomad4 AFR exome

AF:

0.0407

Gnomad4 AMR exome

AF:

0.0853

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.155

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.126

AC:

19159

AN:

152126

Hom.:

1507

Cov.:

AF XY:

0.127

AC XY:

9420

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0487

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0540

Hom.:

Bravo

AF:

0.115

Asia WGS

AF:

0.191

AC:

666

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.1

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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