rs3895894

Variant names:

• chr12-42510776-C-T
• rs3895894
• NM_153026.3:c.-48-38212G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153026.3(PRICKLE1):​c.-48-38212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,004 control chromosomes in the GnomAD database, including 23,251 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23251 hom., cov: 32)
• Consequence: PRICKLE1 NM_153026.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE1	NM_153026.3	MANE Select	c.-48-38212G>A		intron	N/A	NP_694571.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE1	ENST00000345127.9	TSL:1 MANE Select	c.-48-38212G>A		intron	N/A	ENSP00000345064.3
	PRICKLE1	ENST00000547113.1	TSL:1	c.-48-38212G>A		intron	N/A	ENSP00000446699.1
	PRICKLE1	ENST00000640646.1	TSL:1	c.-48-38212G>A		intron	N/A	ENSP00000492483.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82457 AN: 151886 Hom.: 23229 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.546

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.543 AC: 82525 AN: 152004 Hom.: 23251 Cov.: 32 AF XY: 0.543 AC XY: 40314 AN XY: 74292

African (AFR) AF: 0.390 AC: 16156 AN: 41436

American (AMR) AF: 0.558 AC: 8519 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3703 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2746 AN: 4820

European-Finnish (FIN) AF: 0.578 AC: 6095 AN: 10546

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41541 AN: 67976

Other (OTH) AF: 0.548 AC: 1156 AN: 2110

Alfa AF: 0.590 Hom.: 14780

Bravo AF: 0.538

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3895894; hg19: chr12-42904578;