3-189763775-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003722.5(TP63):​c.324+25001G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,998 control chromosomes in the GnomAD database, including 8,177 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 0.32 ( 8177 hom., cov: 32)

Consequence

TP63
NM_003722.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TP63NM_003722.5 linkuse as main transcriptc.324+25001G>A intron_variant ENST00000264731.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TP63ENST00000264731.8 linkuse as main transcriptc.324+25001G>A intron_variant 1 NM_003722.5 P4Q9H3D4-1

Frequencies

GnomAD3 genomes
AF:
0.324
AC:
49180
AN:
151880
Hom.:
8157
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.376
Gnomad AMI
AF:
0.352
Gnomad AMR
AF:
0.281
Gnomad ASJ
AF:
0.290
Gnomad EAS
AF:
0.446
Gnomad SAS
AF:
0.351
Gnomad FIN
AF:
0.355
Gnomad MID
AF:
0.345
Gnomad NFE
AF:
0.287
Gnomad OTH
AF:
0.317
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.324
AC:
49234
AN:
151998
Hom.:
8177
Cov.:
32
AF XY:
0.326
AC XY:
24203
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.377
Gnomad4 AMR
AF:
0.281
Gnomad4 ASJ
AF:
0.290
Gnomad4 EAS
AF:
0.446
Gnomad4 SAS
AF:
0.351
Gnomad4 FIN
AF:
0.355
Gnomad4 NFE
AF:
0.287
Gnomad4 OTH
AF:
0.318
Alfa
AF:
0.293
Hom.:
7144
Bravo
AF:
0.322
Asia WGS
AF:
0.397
AC:
1381
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.54
DANN
Benign
0.53

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6797860; hg19: chr3-189481564; API