rs3747562

Positions:

chr12-42460403-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153026.3(PRICKLE1):c.1902T>C(p.Ser634=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,330 control chromosomes in the GnomAD database, including 157,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15364 hom., cov: 31)

Exomes 𝑓: 0.44 ( 142216 hom. )

Consequence

PRICKLE1
NM_153026.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-42460403-A-G is Benign according to our data. Variant chr12-42460403-A-G is described in ClinVar as [Benign]. Clinvar id is 96506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-42460403-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.458 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.1902T>C	p.Ser634=	synonymous_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.1902T>C	p.Ser634=	synonymous_variant	8/8	1	NM_153026.3	ENSP00000345064	P1
	ENST00000547824.1 linkuse as main transcript	n.1038A>G		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68175

AN:

151520

Hom.:

15345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.418

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.441

GnomAD3 exomes

AF:

0.439

AC:

110302

AN:

251372

Hom.:

24458

AF XY:

0.433

AC XY:

58806

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.467

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.420

Gnomad SAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.439

AC:

642086

AN:

1461690

Hom.:

142216

Cov.:

AF XY:

0.436

AC XY:

317124

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.488

Gnomad4 ASJ exome

AF:

0.450

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.439

GnomAD4 genome

AF:

0.450

AC:

68244

AN:

151640

Hom.:

15364

Cov.:

AF XY:

0.447

AC XY:

33135

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.464

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.453

Gnomad4 EAS

AF:

0.418

Gnomad4 SAS

AF:

0.338

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.440

Alfa

AF:

0.454

Hom.:

24670

Bravo

AF:

0.458

Asia WGS

AF:

0.379

AC:

1321

AN:

3478

EpiCase

AF:

0.455

EpiControl

AF:

0.458

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 02, 2014	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jan 08, 2016	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epilepsy, progressive myoclonic, 1B

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.15

DANN

Benign

0.59

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