Variant X-49177106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006150.5(PRICKLE3):c.1052G>A(p.Arg351His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,199,081 control chromosomes in the GnomAD database, including 1 homozygotes. There are 47 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 1 hom. 44 hem. )

Consequence

PRICKLE3
NM_006150.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.673

Variant links:

Genes affected

PRICKLE3 (HGNC:6645): (prickle planar cell polarity protein 3) LIM domain only 6 is a three LIM domain-containing protein. The LIM domain is a cysteine-rich sequence motif that binds zinc atoms to form a specific protein-binding interface for protein-protein interactions. [provided by RefSeq, Jul 2008]

PRICKLE3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050996423).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE3	NM_006150.5 linkuse as main transcript	c.1052G>A	p.Arg351His	missense_variant	8/9	ENST00000599218.6
PRICKLE3	NM_001307979.2 linkuse as main transcript	c.848G>A	p.Arg283His	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE3	ENST00000599218.6 linkuse as main transcript	c.1052G>A	p.Arg351His	missense_variant	8/9	1	NM_006150.5	P3	O43900-1
PRICKLE3	ENST00000453382.5 linkuse as main transcript	c.848G>A	p.Arg283His	missense_variant	7/8	5		A2
PRICKLE3	ENST00000540849.5 linkuse as main transcript	c.*514G>A		3_prime_UTR_variant, NMD_transcript_variant	7/8	2
PRICKLE3	ENST00000614014.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000889

AC:

AN:

112485

Hom.:

Cov.:

AF XY:

0.0000865

AC XY:

AN XY:

34683

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00292

Gnomad AMR

AF:

0.0000932

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

150521

Hom.:

AF XY:

0.0000209

AC XY:

AN XY:

47797

show subpopulations

Gnomad AFR exome

AF:

0.000103

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.000254

GnomAD4 exome

AF:

0.000137

AC:

149

AN:

1086596

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

355124

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.0000297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.0000889

AC:

AN:

112485

Hom.:

Cov.:

AF XY:

0.0000865

AC XY:

AN XY:

34683

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.0000932

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2023

The c.1052G>A (p.R351H) alteration is located in exon 8 (coding exon 8) of the PRICKLE3 gene. This alteration results from a G to A substitution at nucleotide position 1052, causing the arginine (R) at amino acid position 351 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

D;.

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.68

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.12

B;.

Vest4

0.16

MVP

0.41

ClinPred

0.040

GERP RS

2.0

Varity_R

0.23

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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