Variant X-49177028-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006150.5(PRICKLE3):c.1130C>T(p.Pro377Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,207,814 control chromosomes in the GnomAD database, including 1 homozygotes. There are 142 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.00036 ( 1 hom. 131 hem. )

Consequence

PRICKLE3
NM_006150.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.807

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039325178).

BP6

Variant X-49177028-G-A is Benign according to our data. Variant chrX-49177028-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2507491.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE3	NM_006150.5 linkuse as main transcript	c.1130C>T	p.Pro377Leu	missense_variant	8/9	ENST00000599218.6
PRICKLE3	NM_001307979.2 linkuse as main transcript	c.926C>T	p.Pro309Leu	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE3	ENST00000599218.6 linkuse as main transcript	c.1130C>T	p.Pro377Leu	missense_variant	8/9	1	NM_006150.5	P3	O43900-1
PRICKLE3	ENST00000453382.5 linkuse as main transcript	c.926C>T	p.Pro309Leu	missense_variant	7/8	5		A2
PRICKLE3	ENST00000540849.5 linkuse as main transcript	c.*592C>T		3_prime_UTR_variant, NMD_transcript_variant	7/8	2

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

112579

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

AN XY:

34751

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000372

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000376

Gnomad OTH

AF:

0.000656

GnomAD3 exomes

AF:

0.000428

AC:

AN:

172715

Hom.:

AF XY:

0.000352

AC XY:

AN XY:

59705

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000599

Gnomad ASJ exome

AF:

0.000820

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000673

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.000364

AC:

399

AN:

1095180

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

131

AN XY:

361008

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000429

Gnomad4 ASJ exome

AF:

0.000673

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000112

Gnomad4 FIN exome

AF:

0.0000249

Gnomad4 NFE exome

AF:

0.000401

Gnomad4 OTH exome

AF:

0.000523

GnomAD4 genome

AF:

0.000240

AC:

AN:

112634

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

AN XY:

34816

show subpopulations

Gnomad4 AFR

AF:

0.0000322

Gnomad4 AMR

AF:

0.000372

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000376

Gnomad4 OTH

AF:

0.000648

Alfa

AF:

0.000234

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000363

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.1130C>T (p.P377L) alteration is located in exon 8 (coding exon 8) of the PRICKLE3 gene. This alteration results from a C to T substitution at nucleotide position 1130, causing the proline (P) at amino acid position 377 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

PRICKLE3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.048

T;.

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.47

Sift4G

Uncertain

0.014

D;T

Polyphen

0.18

B;.

Vest4

0.10

MVP

0.23

ClinPred

0.021

GERP RS

2.6

Varity_R

0.044

gMVP

0.20

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