3-189656568-T-A

Position:

• chr3-189656568-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003722.5(TP63):​c.62+24991T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,788 control chromosomes in the GnomAD database, including 16,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (16064 hom., cov: 32)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.565

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-189656568-T-A is Benign according to our data. Variant chr3-189656568-T-A is described in ClinVar as [Benign]. Clinvar id is 1234137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP63	NM_003722.5	c.62+24991T>A		intron_variant		ENST00000264731.8	NP_003713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8	c.62+24991T>A		intron_variant		1	NM_003722.5	ENSP00000264731	P4

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66740 AN: 151672 Hom.: 16046 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66787 AN: 151788 Hom.: 16064 Cov.: 32 AF XY: 0.442 AC XY: 32759 AN XY: 74164

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.509

Alfa AF: 0.481 Hom.: 2256

Bravo AF: 0.441

Asia WGS AF: 0.408 AC: 1411 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4505678; hg19: chr3-189374357;