rs17505102

Variant names:

• chr3-189683987-G-C
• rs17505102
• NM_003722.5:c.62+52410G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-189683987-G-C
• chr3-189683987-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003722.5(TP63):​c.62+52410G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 152,124 control chromosomes in the GnomAD database, including 803 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 0.097 (803 hom., cov: 32)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• Publications: 27 publications found

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 Gene-Disease associations (from GenCC):

• ADULT syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• limb-mammary syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• Rapp-Hodgkin syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• premature ovarian failure 21

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• split hand-foot malformation 4

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• EEC syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• split hand-foot malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP63	NM_003722.5	c.62+52410G>C		intron_variant	Intron 1 of 13	ENST00000264731.8	NP_003713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8	c.62+52410G>C		intron_variant	Intron 1 of 13	1	NM_003722.5	ENSP00000264731.3

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14668 AN: 152006 Hom.: 800 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0703

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0758

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

GnomAD4 genome AF: 0.0965 AC: 14680 AN: 152124 Hom.: 803 Cov.: 32 AF XY: 0.0977 AC XY: 7265 AN XY: 74372

African (AFR) AF: 0.0520 AC: 2158 AN: 41530

American (AMR) AF: 0.0627 AC: 958 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.0701 AC: 363 AN: 5178

South Asian (SAS) AF: 0.161 AC: 773 AN: 4798

European-Finnish (FIN) AF: 0.134 AC: 1418 AN: 10578

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8604 AN: 67984

Other (OTH) AF: 0.0802 AC: 169 AN: 2106

Alfa AF: 0.104 Hom.: 539

Bravo AF: 0.0862

Asia WGS AF: 0.129 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17505102; hg19: chr3-189401776;