Variant rs9840360 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.1349+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,004 control chromosomes in the GnomAD database, including 36,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5115 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31167 hom. )

Consequence

TP63
ENST00000264731.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.66

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=-0.89).

BP6

Variant 3-189873036-G-A is Benign according to our data. Variant chr3-189873036-G-A is described in ClinVar as [Benign]. Clinvar id is 259126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189873036-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 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.1067+41G>A		intron_variant		ENST00000354600.10	NP_001108452.1
TP63	NM_003722.5 linkuse as main transcript	c.1349+41G>A		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.1349+41G>A		intron_variant		1	NM_003722.5	ENSP00000264731	P4	Q9H3D4-1
TP63	ENST00000354600.10 linkuse as main transcript	c.1067+41G>A		intron_variant		1	NM_001114980.2	ENSP00000346614	A1	Q9H3D4-2

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37391

AN:

151796

Hom.:

5111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.202

AC:

50518

AN:

250562

Hom.:

5619

AF XY:

0.204

AC XY:

27666

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.202

AC:

295645

AN:

1461090

Hom.:

31167

Cov.:

AF XY:

0.203

AC XY:

147836

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.198

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.246

AC:

37398

AN:

151914

Hom.:

5115

Cov.:

AF XY:

0.245

AC XY:

18167

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.250

Gnomad4 NFE

AF:

0.197

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.208

Hom.:

678

Bravo

AF:

0.246

Asia WGS

AF:

0.186

AC:

646

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.018

DANN

Benign

0.50

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