Variant X-49176118-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006150.5(PRICKLE3):c.1403G>T(p.Arg468Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

PRICKLE3
NM_006150.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20895606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE3	NM_006150.5 linkuse as main transcript	c.1403G>T	p.Arg468Leu	missense_variant	9/9	ENST00000599218.6	NP_006141.2	O43900-1A0A024QYW5B7Z8D2B7Z5U0
PRICKLE3	NM_001307979.2 linkuse as main transcript	c.1199G>T	p.Arg400Leu	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.1403G>T	p.Arg468Leu	missense_variant	9/9	1	NM_006150.5	ENSP00000470248.1	O43900-1
PRICKLE3	ENST00000453382.5 linkuse as main transcript	c.1199G>T	p.Arg400Leu	missense_variant	8/8	5		ENSP00000388599.2	H0Y413
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*865G>T		non_coding_transcript_exon_variant	8/8	2		ENSP00000446051.2	F5H4N2
PRICKLE3	ENST00000540849.5 linkuse as main transcript	n.*865G>T		3_prime_UTR_variant	8/8	2		ENSP00000446051.2	F5H4N2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000183

AC:

AN:

164019

Hom.:

AF XY:

0.0000176

AC XY:

AN XY:

56777

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000274

AC:

AN:

1093610

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000859

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000469

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.00

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 13, 2023

The c.1403G>T (p.R468L) alteration is located in exon 9 (coding exon 9) of the PRICKLE3 gene. This alteration results from a G to T substitution at nucleotide position 1403, causing the arginine (R) at amino acid position 468 to be replaced by a leucine (L). 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

0.21

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

T;.

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

L;.

PrimateAI

Pathogenic

0.81

Sift4G

Benign

0.35

T;T

Polyphen

0.96

P;.

Vest4

0.39

MVP

0.31

ClinPred

0.38

GERP RS

2.3

Varity_R

0.30

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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