12-42460406-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.1899T>C(p.Phe633Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,382 control chromosomes in the GnomAD database, including 104,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8241 hom., cov: 31)

Exomes 𝑓: 0.36 ( 96623 hom. )

Consequence

PRICKLE1
NM_153026.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.436

Publications

23 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=-0.58).

BP6

Variant 12-42460406-A-G is Benign according to our data. Variant chr12-42460406-A-G is described in ClinVar as Benign. ClinVar VariationId is 130024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.436 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE1	NM_153026.3 link	c.1899T>C	p.Phe633Phe	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.1899T>C	p.Phe633Phe	synonymous_variant	Exon 8 of 8	1	NM_153026.3	ENSP00000345064.3		Q96MT3

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48517

AN:

151562

Hom.:

8233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.324

GnomAD2 exomes

AF:

0.349

AC:

87749

AN:

251368

AF XY:

0.348

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.360

AC:

526194

AN:

1461700

Hom.:

96623

Cov.:

AF XY:

0.358

AC XY:

260349

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.204

AC:

6826

AN:

33478

American (AMR)

AF:

0.397

AC:

17751

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

10044

AN:

26136

East Asian (EAS)

AF:

0.293

AC:

11632

AN:

39700

South Asian (SAS)

AF:

0.255

AC:

21990

AN:

86248

European-Finnish (FIN)

AF:

0.392

AC:

20955

AN:

53418

Middle Eastern (MID)

AF:

0.389

AC:

2245

AN:

5768

European-Non Finnish (NFE)

AF:

0.372

AC:

413704

AN:

1111846

Other (OTH)

AF:

0.349

AC:

21047

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

20554

41108

61662

82216

102770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12826

25652

38478

51304

64130

<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:

0.320

AC:

48551

AN:

151682

Hom.:

8241

Cov.:

AF XY:

0.318

AC XY:

23558

AN XY:

74110

show subpopulations

African (AFR)

AF:

0.204

AC:

8472

AN:

41442

American (AMR)

AF:

0.343

AC:

5217

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1296

AN:

3468

East Asian (EAS)

AF:

0.267

AC:

1369

AN:

5122

South Asian (SAS)

AF:

0.252

AC:

1209

AN:

4798

European-Finnish (FIN)

AF:

0.381

AC:

4006

AN:

10506

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.381

AC:

25849

AN:

67812

Other (OTH)

AF:

0.322

AC:

676

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1638

3276

4914

6552

8190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.358

Hom.:

5157

Bravo

AF:

0.318

Asia WGS

AF:

0.262

AC:

914

AN:

3478

EpiCase

AF:

0.377

EpiControl

AF:

0.379

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 02, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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. -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2018

Athena Diagnostics

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:1

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

-0.58

CADD

Benign

7.2

(source)

DANN

Benign

0.66

PhyloP100

0.44

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