rs1913720

Positions:

• chr3-189857038-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.580-7194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,870 control chromosomes in the GnomAD database, including 13,937 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 0.42 (13937 hom., cov: 32)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP63	NM_001114980.2	c.298-7194A>G		intron_variant		ENST00000354600.10	NP_001108452.1
TP63	NM_003722.5	c.580-7194A>G		intron_variant		ENST00000264731.8	NP_003713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8	c.580-7194A>G		intron_variant		1	NM_003722.5	ENSP00000264731	P4
TP63	ENST00000354600.10	c.298-7194A>G		intron_variant		1	NM_001114980.2	ENSP00000346614	A1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64141 AN: 151752 Hom.: 13941 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.422 AC: 64146 AN: 151870 Hom.: 13937 Cov.: 32 AF XY: 0.416 AC XY: 30893 AN XY: 74256

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.426

Alfa AF: 0.408 Hom.: 1605

Bravo AF: 0.431

Asia WGS AF: 0.312 AC: 1085 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.69

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: rs1913720; hg19: chr3-189574827;