GeneBe

3-189789729-C-CAGAA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000460036.1(TP63):​n.35_36insAGAA variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000225 in 1,332,694 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

TP63
ENST00000460036.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.67

Publications

0 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TP63NM_001114980.2 linkc.-72_-71insAGAA 5_prime_UTR_variant Exon 1 of 12 ENST00000354600.10 NP_001108452.1 Q9H3D4-2
TP63NM_003722.5 linkc.325-18543_325-18542insAGAA intron_variant Intron 3 of 13 ENST00000264731.8 NP_003713.3 Q9H3D4-1A0A0S2Z4N5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TP63ENST00000354600.10 linkc.-72_-71insAGAA 5_prime_UTR_variant Exon 1 of 12 1 NM_001114980.2 ENSP00000346614.5 Q9H3D4-2
TP63ENST00000264731.8 linkc.325-18543_325-18542insAGAA intron_variant Intron 3 of 13 1 NM_003722.5 ENSP00000264731.3 Q9H3D4-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000225
AC:
3
AN:
1332694
Hom.:
0
Cov.:
32
AF XY:
0.00000152
AC XY:
1
AN XY:
658638
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28644
American (AMR)
AF:
0.000100
AC:
3
AN:
29960
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24110
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34066
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71552
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49848
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5504
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1033230
Other (OTH)
AF:
0.00
AC:
0
AN:
55780
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
5.7

Splicing

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

Publications

Other links and lift over

dbSNP: rs34201045; hg19: chr3-189507518; API