12-42510776-C-T

Position:

• chr12-42510776-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE1	NM_153026.3	c.-48-38212G>A		intron_variant		ENST00000345127.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE1	ENST00000345127.9	c.-48-38212G>A		intron_variant		1	NM_153026.3	P1

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

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.548

Alfa AF: 0.590 Hom.: 13398

Bravo AF: 0.538

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs3895894; hg19: chr12-42904578;