12-42484802-T-C

Variant names:

• chr12-42484802-T-C
• rs1796390
• NM_153026.3:c.-48-12238A>G

Variant summary

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

The NM_153026.3(PRICKLE1):​c.-48-12238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,074 control chromosomes in the GnomAD database, including 46,077 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 0.78 (46077 hom., cov: 31)
• Consequence: PRICKLE1 NM_153026.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE1	NM_153026.3	MANE Select	c.-48-12238A>G		intron	N/A	NP_694571.2	Q96MT3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE1	ENST00000345127.9	TSL:1 MANE Select	c.-48-12238A>G		intron	N/A	ENSP00000345064.3	Q96MT3
	PRICKLE1	ENST00000547113.1	TSL:1	c.-48-12238A>G		intron	N/A	ENSP00000446699.1	F8W1Q8
	PRICKLE1	ENST00000640646.1	TSL:1	c.-48-12238A>G		intron	N/A	ENSP00000492483.1	F8W1Q8

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118000 AN: 151956 Hom.: 46034 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.799

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

GnomAD4 genome AF: 0.777 AC: 118097 AN: 152074 Hom.: 46077 Cov.: 31 AF XY: 0.777 AC XY: 57773 AN XY: 74338

African (AFR) AF: 0.825 AC: 34217 AN: 41464

American (AMR) AF: 0.823 AC: 12585 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2851 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3812 AN: 5172

South Asian (SAS) AF: 0.804 AC: 3873 AN: 4818

European-Finnish (FIN) AF: 0.737 AC: 7780 AN: 10556

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50306 AN: 67986

Other (OTH) AF: 0.798 AC: 1688 AN: 2114

Alfa AF: 0.757 Hom.: 35452

Bravo AF: 0.785

Asia WGS AF: 0.781 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		-0.28
PromoterAI		-0.011	Neutral
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: rs1796390; hg19: chr12-42878604;