3-189819732-T-C

Position:

• chr3-189819732-T-C

Variant summary

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

The NM_003722.5(TP63):​c.579+11206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 148,650 control chromosomes in the GnomAD database, including 1,526 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 0.14 (1526 hom., cov: 29)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP63	NM_003722.5	c.579+11206T>C		intron_variant		ENST00000264731.8	NP_003713.3
TP63	NM_001114980.2	c.297+11206T>C		intron_variant		ENST00000354600.10	NP_001108452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8	c.579+11206T>C		intron_variant		1	NM_003722.5	ENSP00000264731.3
TP63	ENST00000354600.10	c.297+11206T>C		intron_variant		1	NM_001114980.2	ENSP00000346614.5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20168 AN: 148556 Hom.: 1521 Cov.: 29

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.136 AC: 20192 AN: 148650 Hom.: 1526 Cov.: 29 AF XY: 0.133 AC XY: 9638 AN XY: 72208

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0638 Hom.: 83

Bravo AF: 0.137

Asia WGS AF: 0.0580 AC: 202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.47

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: rs6795465; hg19: chr3-189537521;