Variant 12-42459548-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153026.3(PRICKLE1):c.*261T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 615,396 control chromosomes in the GnomAD database, including 37,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7719 hom., cov: 32)

Exomes 𝑓: 0.35 ( 29479 hom. )

Consequence

PRICKLE1
NM_153026.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.832

Variant links:

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 links:

(HGNC:):

links:

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]

PPHLN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-42459548-A-G is Benign according to our data. Variant chr12-42459548-A-G is described in ClinVar as [Benign]. Clinvar id is 1293941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE1	NM_153026.3 linkuse as main transcript	c.*261T>C		3_prime_UTR_variant	8/8	ENST00000345127.9	NP_694571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE1	ENST00000345127.9 linkuse as main transcript	c.*261T>C		3_prime_UTR_variant	8/8	1	NM_153026.3	ENSP00000345064	P1
	ENST00000547824.1 linkuse as main transcript	n.183A>G		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45092

AN:

151938

Hom.:

7717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.299

GnomAD4 exome

AF:

0.348

AC:

161202

AN:

463340

Hom.:

29479

Cov.:

AF XY:

0.344

AC XY:

84639

AN XY:

246128

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.371

Gnomad4 ASJ exome

AF:

0.382

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.398

Gnomad4 NFE exome

AF:

0.378

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.297

AC:

45113

AN:

152056

Hom.:

7719

Cov.:

AF XY:

0.297

AC XY:

22049

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.348

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.358

Hom.:

10129

Bravo

AF:

0.289

Asia WGS

AF:

0.219

AC:

767

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over