12-42460406-A-G

Position:

chr12-42460406-A-G

Variant summary

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

The ENST00000345127.9(PRICKLE1):c.1899T>C(p.Phe633=) 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
ENST00000345127.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.436

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=-0.58).

BP6

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

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/exons	MANE	Protein	UniProt
PRICKLE1	NM_153026.3 linkuse as main transcript	c.1899T>C	p.Phe633=	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.1899T>C	p.Phe633=	synonymous_variant	8/8	1	NM_153026.3	ENSP00000345064	P1
	ENST00000547824.1 linkuse as main transcript	n.1041A>G		non_coding_transcript_exon_variant	1/2	1

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

GnomAD3 exomes

AF:

0.349

AC:

87749

AN:

251368

Hom.:

15874

AF XY:

0.348

AC XY:

47223

AN XY:

135854

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 SAS exome

AF:

0.257

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

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.320

AC:

48551

AN:

151682

Hom.:

8241

Cov.:

AF XY:

0.318

AC XY:

23558

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.381

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.359

Hom.:

5144

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

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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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. -
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. -

not provided

Benign:3

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

Epilepsy, progressive myoclonic, 1B

Benign:1

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

-0.58

CADD

Benign

7.2

DANN

Benign

0.66

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