dbSNP rs6790167: TP63:c.1212+79A>G (chr3-189869485-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003722.5(TP63):c.1212+79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,274,402 control chromosomes in the GnomAD database, including 162,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22092 hom., cov: 30)

Exomes 𝑓: 0.50 ( 140404 hom. )

Consequence

TP63
NM_003722.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.760

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-189869485-A-G is Benign according to our data. Variant chr3-189869485-A-G is described in ClinVar as [Benign]. Clinvar id is 1232095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189869485-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP63	NM_003722.5 link	c.1212+79A>G		intron_variant	Intron 9 of 13	ENST00000264731.8	NP_003713.3	Q9H3D4-1A0A0S2Z4N5
TP63	NM_001114980.2 link	c.930+79A>G		intron_variant	Intron 7 of 11	ENST00000354600.10	NP_001108452.1	Q9H3D4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8 link	c.1212+79A>G		intron_variant	Intron 9 of 13	1	NM_003722.5	ENSP00000264731.3		Q9H3D4-1
TP63	ENST00000354600.10 link	c.930+79A>G		intron_variant	Intron 7 of 11	1	NM_001114980.2	ENSP00000346614.5		Q9H3D4-2

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80408

AN:

151790

Hom.:

22072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.682

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.495

AC:

555891

AN:

1122494

Hom.:

140404

AF XY:

0.491

AC XY:

279916

AN XY:

569828

show subpopulations

Gnomad4 AFR exome

AF:

0.677

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.422

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.402

Gnomad4 NFE exome

AF:

0.511

Gnomad4 OTH exome

AF:

0.506

GnomAD4 genome

AF:

0.530

AC:

80467

AN:

151908

Hom.:

22092

Cov.:

AF XY:

0.520

AC XY:

38626

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.667

Gnomad4 AMR

AF:

0.444

Gnomad4 ASJ

AF:

0.509

Gnomad4 EAS

AF:

0.395

Gnomad4 SAS

AF:

0.394

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.505

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.516

Hom.:

20958

Bravo

AF:

0.541

Asia WGS

AF:

0.390

AC:

1361

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.38

DANN

Benign

0.40

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over