Variant rs35558939 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.1652+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 1,613,628 control chromosomes in the GnomAD database, including 1,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 89 hom., cov: 33)

Exomes 𝑓: 0.041 ( 1353 hom. )

Consequence

TP63
NM_003722.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0130

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=-0.64).

BP6

Variant 3-189889530-G-A is Benign according to our data. Variant chr3-189889530-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189889530-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.06 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.1370+46G>A		intron_variant		ENST00000354600.10	NP_001108452.1
TP63	NM_003722.5 linkuse as main transcript	c.1652+46G>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.1652+46G>A		intron_variant		1	NM_003722.5	ENSP00000264731	P4	Q9H3D4-1
TP63	ENST00000354600.10 linkuse as main transcript	c.1370+46G>A		intron_variant		1	NM_001114980.2	ENSP00000346614	A1	Q9H3D4-2

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4686

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00967

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0487

GnomAD3 exomes

AF:

0.0324

AC:

8086

AN:

249466

Hom.:

176

AF XY:

0.0335

AC XY:

4513

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.00794

Gnomad AMR exome

AF:

0.0226

Gnomad ASJ exome

AF:

0.0535

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.0252

Gnomad NFE exome

AF:

0.0476

Gnomad OTH exome

AF:

0.0389

GnomAD4 exome

AF:

0.0414

AC:

60459

AN:

1461294

Hom.:

1353

Cov.:

AF XY:

0.0409

AC XY:

29750

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.00995

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.0524

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0185

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.0467

Gnomad4 OTH exome

AF:

0.0410

GnomAD4 genome

AF:

0.0308

AC:

4686

AN:

152334

Hom.:

Cov.:

AF XY:

0.0301

AC XY:

2242

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00969

Gnomad4 AMR

AF:

0.0303

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0161

Gnomad4 FIN

AF:

0.0213

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0477

Alfa

AF:

0.0426

Hom.:

Bravo

AF:

0.0313

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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