chr12-42460403-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153026.3(PRICKLE1):c.1902T>C(p.Ser634Ser) 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

Publications

43 publications found

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 Gene-Disease associations (from GenCC):

epilepsy, progressive myoclonic, 1B
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Unverricht-Lundborg syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
progressive myoclonus epilepsy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

PRICKLE1 links:

ENSG00000257225 (HGNC:58444):

ENSG00000257225 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 96506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PRICKLE1	NM_153026.3 link	c.1902T>C	p.Ser634Ser	synonymous_variant	Exon 8 of 8	ENST00000345127.9	NP_694571.2	Q96MT3A0A024R0W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE1	ENST00000345127.9 link	c.1902T>C	p.Ser634Ser	synonymous_variant	Exon 8 of 8	1	NM_153026.3	ENSP00000345064.3		Q96MT3

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

GnomAD2 exomes

AF:

0.439

AC:

110302

AN:

251372

AF XY:

0.433

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 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

African (AFR)

AF:

0.469

AC:

15707

AN:

33478

American (AMR)

AF:

0.488

AC:

21805

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

11752

AN:

26136

East Asian (EAS)

AF:

0.405

AC:

16082

AN:

39700

South Asian (SAS)

AF:

0.330

AC:

28494

AN:

86250

European-Finnish (FIN)

AF:

0.428

AC:

22880

AN:

53416

Middle Eastern (MID)

AF:

0.475

AC:

2741

AN:

5768

European-Non Finnish (NFE)

AF:

0.446

AC:

496097

AN:

1111834

Other (OTH)

AF:

0.439

AC:

26528

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

21975

43951

65926

87902

109877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14842

29684

44526

59368

74210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.450

AC:

68244

AN:

151640

Hom.:

15364

Cov.:

AF XY:

0.447

AC XY:

33135

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.464

AC:

19187

AN:

41374

American (AMR)

AF:

0.466

AC:

7102

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

1570

AN:

3468

East Asian (EAS)

AF:

0.418

AC:

2141

AN:

5128

South Asian (SAS)

AF:

0.338

AC:

1622

AN:

4792

European-Finnish (FIN)

AF:

0.418

AC:

4388

AN:

10508

Middle Eastern (MID)

AF:

0.466

AC:

136

AN:

292

European-Non Finnish (NFE)

AF:

0.454

AC:

30786

AN:

67832

Other (OTH)

AF:

0.440

AC:

926

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1930

3860

5790

7720

9650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.454

Hom.:

44675

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

Jul 02, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Epilepsy, progressive myoclonic, 1B

Benign:2

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.15

(source)

DANN

Benign

0.59

PhyloP100

-2.2

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over