rs144843013

Variant names:

• chr12-42470315-G-A
• rs144843013
• NM_153026.3:c.177C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_153026.3(PRICKLE1):​c.177C>T​(p.Tyr59Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,613,942 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (33 hom.)
• Consequence: PRICKLE1 NM_153026.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.151
• Publications: 2 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 12-42470315-G-A is Benign according to our data. Variant chr12-42470315-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.151 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

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.177C>T	p.Tyr59Tyr	synonymous	Exon 3 of 8	NP_694571.2	Q96MT3
	PRICKLE1	NM_001144881.2		c.177C>T	p.Tyr59Tyr	synonymous	Exon 3 of 8	NP_001138353.1	Q96MT3
	PRICKLE1	NM_001144882.2		c.177C>T	p.Tyr59Tyr	synonymous	Exon 3 of 8	NP_001138354.1	Q96MT3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE1	ENST00000345127.9	TSL:1 MANE Select	c.177C>T	p.Tyr59Tyr	synonymous	Exon 3 of 8	ENSP00000345064.3	Q96MT3
	PRICKLE1	ENST00000547113.1	TSL:1	c.177C>T	p.Tyr59Tyr	synonymous	Exon 3 of 4	ENSP00000446699.1	F8W1Q8
	PRICKLE1	ENST00000640646.1	TSL:1	c.177C>T	p.Tyr59Tyr	synonymous	Exon 4 of 5	ENSP00000492483.1	F8W1Q8

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 293 AN: 152118 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00353 AC: 887 AN: 251274 AF XY: 0.00433

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00235

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00282 AC: 4126 AN: 1461706 Hom.: 33 Cov.: 30 AF XY: 0.00328 AC XY: 2387 AN XY: 727170

African (AFR) AF: 0.000209 AC: 7 AN: 33476

American (AMR) AF: 0.00349 AC: 156 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0156 AC: 1342 AN: 86256

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53382

Middle Eastern (MID) AF: 0.00988 AC: 57 AN: 5768

European-Non Finnish (NFE) AF: 0.00214 AC: 2379 AN: 1111878

Other (OTH) AF: 0.00270 AC: 163 AN: 60390

GnomAD4 genome AF: 0.00193 AC: 294 AN: 152236 Hom.: 2 Cov.: 32 AF XY: 0.00207 AC XY: 154 AN XY: 74446

African (AFR) AF: 0.000337 AC: 14 AN: 41542

American (AMR) AF: 0.00236 AC: 36 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4828

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00234 AC: 159 AN: 68020

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00193 Hom.: 0

Bravo AF: 0.00161

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00409

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Epilepsy, progressive myoclonic, 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.0
DANN	Benign	0.85
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism

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: rs144843013; hg19: chr12-42864117; COSMIC: COSV61544397; COSMIC: COSV61544397;