chr12-42459195-C-T

Variant names:

• chr12-42459195-C-T
• rs886049372
• NM_153026.3:c.*614G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153026.3(PRICKLE1):​c.*614G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 678,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: PRICKLE1 NM_153026.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• Publications: 0 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]

PPHLN1 (HGNC:19369): (periphilin 1) The protein encoded by this gene is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ENSG00000257225 (HGNC:58444):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

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.*614G>A		3_prime_UTR	Exon 8 of 8	NP_694571.2	Q96MT3
	PRICKLE1	NM_001144881.2		c.*614G>A		3_prime_UTR	Exon 8 of 8	NP_001138353.1	Q96MT3
	PRICKLE1	NM_001144882.2		c.*614G>A		3_prime_UTR	Exon 8 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.*614G>A		3_prime_UTR	Exon 8 of 8	ENSP00000345064.3	Q96MT3
	PRICKLE1	ENST00000445766.7	TSL:5	c.*614G>A		3_prime_UTR	Exon 8 of 8	ENSP00000398947.2	Q96MT3
	PRICKLE1	ENST00000455697.6	TSL:5	c.*614G>A		3_prime_UTR	Exon 9 of 9	ENSP00000401060.1	Q96MT3

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151422 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.0000322 AC: 17 AN: 527412 Hom.: 0 Cov.: 0 AF XY: 0.0000385 AC XY: 11 AN XY: 286024

African (AFR) AF: 0.0000690 AC: 1 AN: 14484

American (AMR) AF: 0.00 AC: 0 AN: 30172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18750

East Asian (EAS) AF: 0.00 AC: 0 AN: 31920

South Asian (SAS) AF: 0.0000339 AC: 2 AN: 58922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32126

Middle Eastern (MID) AF: 0.000320 AC: 1 AN: 3122

European-Non Finnish (NFE) AF: 0.0000357 AC: 11 AN: 308554

Other (OTH) AF: 0.0000681 AC: 2 AN: 29362

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151534 Hom.: 0 Cov.: 33 AF XY: 0.0000541 AC XY: 4 AN XY: 74002

African (AFR) AF: 0.0000242 AC: 1 AN: 41304

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67944

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Epilepsy, progressive myoclonic, 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		1.5

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: rs886049372; hg19: chr12-42852997;