chr3-189763775-G-A

Position:

• chr3-189763775-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003722.5(TP63):​c.324+25001G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,998 control chromosomes in the GnomAD database, including 8,177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8177 hom., cov: 32)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP63	NM_003722.5	c.324+25001G>A		intron_variant		ENST00000264731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP63	ENST00000264731.8	c.324+25001G>A		intron_variant		1	NM_003722.5	P4

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49180 AN: 151880 Hom.: 8157 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.324 AC: 49234 AN: 151998 Hom.: 8177 Cov.: 32 AF XY: 0.326 AC XY: 24203 AN XY: 74286

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.318

Alfa AF: 0.293 Hom.: 7144

Bravo AF: 0.322

Asia WGS AF: 0.397 AC: 1381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6797860; hg19: chr3-189481564;