Variant X-49177005-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.1153G>A(p.Gly385Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,209,015 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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 0.00012 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000047 ( 0 hom. 11 hem. )

Consequence

PRICKLE3
NM_006150.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.221

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=0.027023017).

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE3	NM_006150.5 linkuse as main transcript	c.1153G>A	p.Gly385Ser	missense_variant	8/9	ENST00000599218.6
PRICKLE3	NM_001307979.2 linkuse as main transcript	c.949G>A	p.Gly317Ser	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE3	ENST00000599218.6 linkuse as main transcript	c.1153G>A	p.Gly385Ser	missense_variant	8/9	1	NM_006150.5	P3	O43900-1
PRICKLE3	ENST00000453382.5 linkuse as main transcript	c.949G>A	p.Gly317Ser	missense_variant	7/8	5		A2
PRICKLE3	ENST00000540849.5 linkuse as main transcript	c.*615G>A		3_prime_UTR_variant, NMD_transcript_variant	7/8	2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

112384

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34590

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

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:

0.0000188

Gnomad OTH

AF:

0.000659

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

177440

Hom.:

AF XY:

0.0000477

AC XY:

AN XY:

62910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000259

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000162

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000127

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1096581

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

362149

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000273

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000125

AC:

AN:

112434

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34650

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.000651

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000212

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

Nov 06, 2023

The c.1153G>A (p.G385S) 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 1153, causing the glycine (G) at amino acid position 385 to be replaced by a serine (S). 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

0.071

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.5

DANN

Benign

0.95

DEOGEN2

Benign

0.020

T;.

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.55

Sift4G

Benign

0.19

T;T

Polyphen

0.51

P;.

Vest4

0.022

MutPred

0.20

Gain of glycosylation at G385 (P = 0.0029);.;

MVP

0.23

ClinPred

0.014

GERP RS

1.8

Varity_R

0.082

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