NM_003722.5:c.1350-34T>G

Variant names:

• chr3-189886360-T-G
• rs1554131
• NM_003722.5:c.1350-34T>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003722.5(TP63):​c.1350-34T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,606,346 control chromosomes in the GnomAD database, including 474,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42393 hom., cov: 32)
  • Exomes 𝑓: 0.77 (431974 hom.)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.91

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-189886360-T-G is Benign according to our data. Variant chr3-189886360-T-G is described in ClinVar as [Benign]. Clinvar id is 259128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189886360-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP63	NM_003722.5	c.1350-34T>G		intron_variant	Intron 10 of 13	ENST00000264731.8	NP_003713.3
TP63	NM_001114980.2	c.1068-34T>G		intron_variant	Intron 8 of 11	ENST00000354600.10	NP_001108452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP63	ENST00000264731.8	c.1350-34T>G		intron_variant	Intron 10 of 13	1	NM_003722.5	ENSP00000264731.3
TP63	ENST00000354600.10	c.1068-34T>G		intron_variant	Intron 8 of 11	1	NM_001114980.2	ENSP00000346614.5

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113016 AN: 151940 Hom.: 42376 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.763

GnomAD3 exomes AF: 0.710 AC: 177842 AN: 250366 Hom.: 64647 AF XY: 0.722 AC XY: 97784 AN XY: 135406

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.595

Gnomad SAS exome AF: 0.718

Gnomad FIN exome AF: 0.696

Gnomad NFE exome AF: 0.789

Gnomad OTH exome AF: 0.737

GnomAD4 exome AF: 0.768 AC: 1116942 AN: 1454288 Hom.: 431974 Cov.: 34 AF XY: 0.768 AC XY: 556275 AN XY: 723900

Gnomad4 AFR exome AF: 0.744

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.635

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.703

Gnomad4 NFE exome AF: 0.793

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.744 AC: 113072 AN: 152058 Hom.: 42393 Cov.: 32 AF XY: 0.734 AC XY: 54586 AN XY: 74328

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.758

Alfa AF: 0.779 Hom.: 73982

Bravo AF: 0.736

Asia WGS AF: 0.656 AC: 2285 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

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	-0.91
CADD	Benign	0.032
DANN	Benign	0.67

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: rs1554131; hg19: chr3-189604149;