Variant 12-42459256-GT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_153026.3(PRICKLE1):c.*552del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.80 ( 48078 hom., cov: 0)

Exomes 𝑓: 0.69 ( 89322 hom. )

Consequence

PRICKLE1
NM_153026.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

PRICKLE1 (HGNC:17019): (prickle planar cell polarity protein 1) This gene encodes a nuclear receptor that may be a negative regulator of the Wnt/beta-catenin signaling pathway. The encoded protein localizes to the nuclear membrane and has been implicated in the nuclear trafficking of the transcription repressors REST/NRSF and REST4. Mutations in this gene have been linked to progressive myoclonus epilepsy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2009]

PRICKLE1 links:

PPHLN1 (HGNC:19369): (periphilin 1) The protein encoded by this gene is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PPHLN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE1	NM_153026.3 linkuse as main transcript	c.*552del		3_prime_UTR_variant	8/8	ENST00000345127.9	NP_694571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE1	ENST00000345127.9 linkuse as main transcript	c.*552del		3_prime_UTR_variant	8/8	1	NM_153026.3	ENSP00000345064	P1

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

119254

AN:

148416

Hom.:

48040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.917

Gnomad AMR

AF:

0.779

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.828

Gnomad NFE

AF:

0.852

Gnomad OTH

AF:

0.783

GnomAD4 exome

AF:

0.689

AC:

303638

AN:

440976

Hom.:

89322

Cov.:

AF XY:

0.688

AC XY:

164676

AN XY:

239342

show subpopulations

Gnomad4 AFR exome

AF:

0.613

Gnomad4 AMR exome

AF:

0.631

Gnomad4 ASJ exome

AF:

0.661

Gnomad4 EAS exome

AF:

0.675

Gnomad4 SAS exome

AF:

0.655

Gnomad4 FIN exome

AF:

0.727

Gnomad4 NFE exome

AF:

0.704

Gnomad4 OTH exome

AF:

0.684

GnomAD4 genome

AF:

0.804

AC:

119350

AN:

148524

Hom.:

48078

Cov.:

AF XY:

0.805

AC XY:

58190

AN XY:

72258

show subpopulations

Gnomad4 AFR

AF:

0.721

Gnomad4 AMR

AF:

0.779

Gnomad4 ASJ

AF:

0.792

Gnomad4 EAS

AF:

0.804

Gnomad4 SAS

AF:

0.782

Gnomad4 FIN

AF:

0.862

Gnomad4 NFE

AF:

0.852

Gnomad4 OTH

AF:

0.781

Asia WGS

AF:

0.735

AC:

2557

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epilepsy, progressive myoclonic, 1B

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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