Variant X-49175932-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.1589G>A(p.Arg530His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,208,816 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000026 ( 0 hom. 10 hem. )

Consequence

PRICKLE3
NM_006150.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500

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=0.025825262).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE3	NM_006150.5 linkuse as main transcript	c.1589G>A	p.Arg530His	missense_variant	9/9	ENST00000599218.6	NP_006141.2	O43900-1A0A024QYW5B7Z8D2B7Z5U0
PRICKLE3	NM_001307979.2 linkuse as main transcript	c.1385G>A	p.Arg462His	missense_variant	9/9		NP_001294908.1	H0Y413B7Z8D2B7Z5U0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRICKLE3	ENST00000599218.6 linkuse as main transcript	c.1589G>A	p.Arg530His	missense_variant	9/9	1	NM_006150.5	ENSP00000470248.1	O43900-1
PRICKLE3	ENST00000453382.5 linkuse as main transcript	c.1385G>A	p.Arg462His	missense_variant	8/8	5		ENSP00000388599.2	H0Y413
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*1051G>A		non_coding_transcript_exon_variant	8/8	2		ENSP00000446051.2	F5H4N2
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*1051G>A		3_prime_UTR_variant	8/8	2		ENSP00000446051.2	F5H4N2

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110650

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

32888

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00152

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000329

AC:

AN:

182214

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

67068

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000807

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1098166

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

363524

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000619

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110650

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

32888

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00152

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000412

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

Nov 29, 2023

The c.1589G>A (p.R530H) alteration is located in exon 9 (coding exon 9) of the PRICKLE3 gene. This alteration results from a G to A substitution at nucleotide position 1589, causing the arginine (R) at amino acid position 530 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

0.070

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.9

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;.

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.29

Sift4G

Benign

0.17

T;T

Polyphen

0.82

P;.

Vest4

0.064

MutPred

0.25

Loss of MoRF binding (P = 0.0468);.;

MVP

0.32

ClinPred

0.060

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.19

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