Variant chrX-49175699-G-C 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.1822C>G(p.Arg608Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,209,476 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 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 0.00016 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000043 ( 0 hom. 18 hem. )

Consequence

PRICKLE3
NM_006150.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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=0.07170412).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE3	NM_006150.5 linkuse as main transcript	c.1822C>G	p.Arg608Gly	missense_variant	9/9	ENST00000599218.6	NP_006141.2	O43900-1A0A024QYW5B7Z8D2B7Z5U0
PRICKLE3	NM_001307979.2 linkuse as main transcript	c.1618C>G	p.Arg540Gly	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.1822C>G	p.Arg608Gly	missense_variant	9/9	1	NM_006150.5	ENSP00000470248.1	O43900-1
PRICKLE3	ENST00000453382.5 linkuse as main transcript	c.1618C>G	p.Arg540Gly	missense_variant	8/8	5		ENSP00000388599.2	H0Y413
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*1284C>G		non_coding_transcript_exon_variant	8/8	2		ENSP00000446051.2	F5H4N2
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*1284C>G		3_prime_UTR_variant	8/8	2		ENSP00000446051.2	F5H4N2

Frequencies

GnomAD3 genomes

AF:

0.000161

AC:

AN:

111972

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34128

show subpopulations

Gnomad AFR

AF:

0.000552

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000660

AC:

AN:

181812

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66510

show subpopulations

Gnomad AFR exome

AF:

0.000535

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000265

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000428

AC:

AN:

1097504

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

362902

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000388

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000594

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.000161

AC:

AN:

111972

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34128

show subpopulations

Gnomad4 AFR

AF:

0.000552

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000370

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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

Mar 22, 2023

The c.1822C>G (p.R608G) alteration is located in exon 9 (coding exon 9) of the PRICKLE3 gene. This alteration results from a C to G substitution at nucleotide position 1822, causing the arginine (R) at amino acid position 608 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.057

T;.

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.72

T;T

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.0

M;.

PrimateAI

Uncertain

0.50

Sift4G

Uncertain

0.025

D;D

Polyphen

0.96

P;.

Vest4

0.19

MVP

0.28

ClinPred

0.052

GERP RS

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.33

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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