Variant chr12-42459718-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153026.3(PRICKLE1):c.*91T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,478,296 control chromosomes in the GnomAD database, including 308,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34650 hom., cov: 33)

Exomes 𝑓: 0.64 ( 273475 hom. )

Consequence

PRICKLE1
NM_153026.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.407

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:

(HGNC:):

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 12-42459718-A-G is Benign according to our data. Variant chr12-42459718-A-G is described in ClinVar as [Benign]. Clinvar id is 1291049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 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.*91T>C		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.*91T>C		3_prime_UTR_variant	8/8	1	NM_153026.3	ENSP00000345064	P1
	ENST00000547824.1 linkuse as main transcript	n.353A>G		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101919

AN:

152032

Hom.:

34605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.731

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.677

GnomAD4 exome

AF:

0.640

AC:

848704

AN:

1326146

Hom.:

273475

Cov.:

AF XY:

0.642

AC XY:

428271

AN XY:

666970

show subpopulations

Gnomad4 AFR exome

AF:

0.755

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.618

Gnomad4 EAS exome

AF:

0.707

Gnomad4 SAS exome

AF:

0.747

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.628

Gnomad4 OTH exome

AF:

0.650

GnomAD4 genome

AF:

0.671

AC:

102022

AN:

152150

Hom.:

34650

Cov.:

AF XY:

0.673

AC XY:

50071

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.658

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.732

Gnomad4 SAS

AF:

0.751

Gnomad4 FIN

AF:

0.616

Gnomad4 NFE

AF:

0.620

Gnomad4 OTH

AF:

0.679

Alfa

AF:

0.636

Hom.:

12382

Bravo

AF:

0.673

Asia WGS

AF:

0.743

AC:

2580

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.79

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