12-42465786-C-T

Variant names:

• chr12-42465786-C-T
• rs11832772
• ENST00000547824.1:n.2449C>T

Variant summary

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

The ENST00000547824.1(ENSG00000257225):​n.2449C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 318,416 control chromosomes in the GnomAD database, including 31,613 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 0.45 (15290 hom., cov: 32)
  • Exomes 𝑓: 0.44 (16323 hom.)
• Consequence: ENSG00000257225 ENST00000547824.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 21 publications found

Genes affected

ENSG00000257225 (HGNC:58444):

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE1	NM_153026.3	c.775+408G>A		intron_variant	Intron 6 of 7	ENST00000345127.9	NP_694571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE1	ENST00000345127.9	c.775+408G>A		intron_variant	Intron 6 of 7	1	NM_153026.3	ENSP00000345064.3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67989 AN: 151872 Hom.: 15273 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.437 AC: 72753 AN: 166424 Hom.: 16323 Cov.: 0 AF XY: 0.427 AC XY: 38207 AN XY: 89452

African (AFR) AF: 0.473 AC: 2297 AN: 4852

American (AMR) AF: 0.479 AC: 2969 AN: 6198

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 2012 AN: 4430

East Asian (EAS) AF: 0.428 AC: 3015 AN: 7040

South Asian (SAS) AF: 0.336 AC: 9314 AN: 27760

European-Finnish (FIN) AF: 0.446 AC: 3438 AN: 7716

Middle Eastern (MID) AF: 0.441 AC: 282 AN: 640

European-Non Finnish (NFE) AF: 0.460 AC: 45717 AN: 99360

Other (OTH) AF: 0.440 AC: 3709 AN: 8428

GnomAD4 genome AF: 0.448 AC: 68056 AN: 151992 Hom.: 15290 Cov.: 32 AF XY: 0.445 AC XY: 33041 AN XY: 74284

African (AFR) AF: 0.460 AC: 19061 AN: 41440

American (AMR) AF: 0.462 AC: 7055 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1567 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2155 AN: 5154

South Asian (SAS) AF: 0.335 AC: 1612 AN: 4814

European-Finnish (FIN) AF: 0.418 AC: 4410 AN: 10540

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30757 AN: 67972

Other (OTH) AF: 0.436 AC: 921 AN: 2114

Alfa AF: 0.448 Hom.: 13088

Bravo AF: 0.454

Asia WGS AF: 0.376 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		0.42
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: rs11832772; hg19: chr12-42859588;