Variant chrX-49175707-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006150.5(PRICKLE3):c.1814G>C(p.Arg605Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,209,724 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 51 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 49 hem. )

Consequence

PRICKLE3
NM_006150.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13257161).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE3	NM_006150.5 linkuse as main transcript	c.1814G>C	p.Arg605Pro	missense_variant	9/9	ENST00000599218.6	NP_006141.2	O43900-1A0A024QYW5B7Z8D2B7Z5U0
PRICKLE3	NM_001307979.2 linkuse as main transcript	c.1610G>C	p.Arg537Pro	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.1814G>C	p.Arg605Pro	missense_variant	9/9	1	NM_006150.5	ENSP00000470248.1	O43900-1
PRICKLE3	ENST00000453382.5 linkuse as main transcript	c.1610G>C	p.Arg537Pro	missense_variant	8/8	5		ENSP00000388599.2	H0Y413
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*1276G>C		non_coding_transcript_exon_variant	8/8	2		ENSP00000446051.2	F5H4N2
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*1276G>C		3_prime_UTR_variant	8/8	2		ENSP00000446051.2	F5H4N2

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

111926

Hom.:

Cov.:

AF XY:

0.0000587

AC XY:

AN XY:

34088

show subpopulations

Gnomad AFR

AF:

0.0000974

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:

0.0000565

Gnomad OTH

AF:

0.000661

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

182381

Hom.:

AF XY:

0.0000448

AC XY:

AN XY:

66991

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.0000528

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000737

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

145

AN:

1097748

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

363136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000163

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.0000625

AC:

AN:

111976

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34148

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.000653

Bravo

AF:

0.0000227

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Dec 27, 2023

The c.1814G>C (p.R605P) alteration is located in exon 9 (coding exon 9) of the PRICKLE3 gene. This alteration results from a G to C substitution at nucleotide position 1814, causing the arginine (R) at amino acid position 605 to be replaced by a proline (P). 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

0.10

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.022

T;.

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.060

.;N

Sift

Uncertain

0.010

.;D

Sift4G

Uncertain

0.039

D;D

Polyphen

1.0

D;.

Vest4

0.24

MVP

0.31

ClinPred

0.086

GERP RS

3.7

Varity_R

0.31

gMVP

0.40

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