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GeneBe

X-49176948-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006150.5(PRICKLE3):​c.1210G>A​(p.Ala404Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,205,321 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A404V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000011 ( 0 hom. 8 hem. )

Consequence

PRICKLE3
NM_006150.5 missense

Scores

1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.047181755).
BS2
High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRICKLE3NM_006150.5 linkuse as main transcriptc.1210G>A p.Ala404Thr missense_variant 8/9 ENST00000599218.6
PRICKLE3NM_001307979.2 linkuse as main transcriptc.1006G>A p.Ala336Thr missense_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRICKLE3ENST00000599218.6 linkuse as main transcriptc.1210G>A p.Ala404Thr missense_variant 8/91 NM_006150.5 P3O43900-1
PRICKLE3ENST00000453382.5 linkuse as main transcriptc.1006G>A p.Ala336Thr missense_variant 7/85 A2
PRICKLE3ENST00000540849.5 linkuse as main transcriptc.*672G>A 3_prime_UTR_variant, NMD_transcript_variant 7/82

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112132
Hom.:
0
Cov.:
23
AF XY:
0.0000291
AC XY:
1
AN XY:
34336
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000730
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000229
AC:
4
AN:
174467
Hom.:
0
AF XY:
0.0000330
AC XY:
2
AN XY:
60697
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000228
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
12
AN:
1093189
Hom.:
0
Cov.:
31
AF XY:
0.0000222
AC XY:
8
AN XY:
359791
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000206
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
AF:
0.0000178
AC:
2
AN:
112132
Hom.:
0
Cov.:
23
AF XY:
0.0000291
AC XY:
1
AN XY:
34336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000730
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJul 20, 2021The c.1210G>A (p.A404T) 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 1210, causing the alanine (A) at amino acid position 404 to be replaced by a threonine (T). 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
0.061
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
4.0
DANN
Benign
0.68
DEOGEN2
Benign
0.018
T;.
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.41
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.047
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.51
T
Sift4G
Benign
0.59
T;T
Polyphen
0.0
B;.
Vest4
0.018
MutPred
0.23
Gain of loop (P = 0.0045);.;
MVP
0.18
ClinPred
0.029
T
GERP RS
0.37
Varity_R
0.050
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.

Other links and lift over

dbSNP: rs782586457; hg19: chrX-49033297; API