rs1515490

chr3-189879066-A-G

Variant summary

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

The NM_003722.5(TP63):c.1349+6071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,292 control chromosomes in the GnomAD database, including 2,492 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 0.16 (2492 hom., cov: 32)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP63	NM_001114980.2	c.1067+6071A>G		intron_variant		ENST00000354600.10
TP63	NM_003722.5	c.1349+6071A>G		intron_variant		ENST00000264731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP63	ENST00000264731.8	c.1349+6071A>G		intron_variant		1	NM_003722.5	P4
TP63	ENST00000354600.10	c.1067+6071A>G		intron_variant		1	NM_001114980.2	A1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24595 AN: 152174 Hom.: 2494 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.161 AC: 24592 AN: 152292 Hom.: 2492 Cov.: 32 AF XY: 0.157 AC XY: 11653 AN XY: 74448

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.190

Alfa AF: 0.202 Hom.: 2571

Bravo AF: 0.164

Asia WGS AF: 0.122 AC: 428 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs1515490; hg19: chr3-189596855;