chrX-49176947-G-A

Position:

• chrX-49176947-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006150.5(PRICKLE3):​c.1211C>T​(p.Ala404Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,148 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PRICKLE3 NM_006150.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.536

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056509554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE3	NM_006150.5	c.1211C>T	p.Ala404Val	missense_variant	8/9	ENST00000599218.6	NP_006141.2
PRICKLE3	NM_001307979.2	c.1007C>T	p.Ala336Val	missense_variant	8/9		NP_001294908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE3	ENST00000599218.6	c.1211C>T	p.Ala404Val	missense_variant	8/9	1	NM_006150.5	ENSP00000470248.1
PRICKLE3	ENST00000453382.5	c.1007C>T	p.Ala336Val	missense_variant	7/8	5		ENSP00000388599.2
PRICKLE3	ENST00000540849.5	n.*673C>T		non_coding_transcript_exon_variant	7/8	2		ENSP00000446051.2
PRICKLE3	ENST00000540849.5	n.*673C>T		3_prime_UTR_variant	7/8	2		ENSP00000446051.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093148 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 359766

Gnomad4 AFR exome AF: 0.0000383

Gnomad4 AMR exome AF: 0.00

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.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.1211C>T (p.A404V) 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 1211, causing the alanine (A) at amino acid position 404 to be replaced by a valine (V). 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	0.068
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.4
DANN	Benign	0.50
DEOGEN2	Benign	0.028	T;.
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;.
Vest4		0.032
MutPred		0.25		Loss of helix (P = 0.0076);.;
MVP		0.15
ClinPred		0.016	T
GERP RS		-3.1
Varity_R		0.040
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49033296;