dbSNP rs147268650: PRICKLE1:p.Val36Val (chr12-42472409-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_153026.3(PRICKLE1):c.108C>T(p.Val36Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,614,088 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V36V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 23 hom. )

Consequence

PRICKLE1
NM_153026.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.00

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 12-42472409-G-A is Benign according to our data. Variant chr12-42472409-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 23 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153026.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRICKLE1	NM_153026.3	MANE Select	c.108C>T	p.Val36Val	synonymous	Exon 2 of 8	NP_694571.2	Q96MT3
PRICKLE1	NM_001144881.2		c.108C>T	p.Val36Val	synonymous	Exon 2 of 8	NP_001138353.1	Q96MT3
PRICKLE1	NM_001144882.2		c.108C>T	p.Val36Val	synonymous	Exon 2 of 8	NP_001138354.1	Q96MT3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRICKLE1	ENST00000345127.9	TSL:1 MANE Select	c.108C>T	p.Val36Val	synonymous	Exon 2 of 8	ENSP00000345064.3	Q96MT3
PRICKLE1	ENST00000547113.1	TSL:1	c.108C>T	p.Val36Val	synonymous	Exon 2 of 4	ENSP00000446699.1	F8W1Q8
PRICKLE1	ENST00000640646.1	TSL:1	c.108C>T	p.Val36Val	synonymous	Exon 3 of 5	ENSP00000492483.1	F8W1Q8

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

564

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00597

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00329

AC:

827

AN:

251166

AF XY:

0.00331

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00574

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00464

AC:

6781

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

3311

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33480

American (AMR)

AF:

0.000939

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.00298

AC:

257

AN:

86254

European-Finnish (FIN)

AF:

0.00120

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00548

AC:

6097

AN:

1111984

Other (OTH)

AF:

0.00430

AC:

260

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

348

696

1043

1391

1739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

220

440

660

880

1100

<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:

0.00370

AC:

564

AN:

152246

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

252

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41542

American (AMR)

AF:

0.00281

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00228

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00597

AC:

406

AN:

68008

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

113

141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00433

Hom.:

Bravo

AF:

0.00361

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00498

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Epilepsy, progressive myoclonic, 1B (1)

PRICKLE1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.17

(source)

DANN

Benign

0.62

PhyloP100

-4.0

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over