X-49176923-G-A

Position:

• chrX-49176923-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006150.5(PRICKLE3):​c.1235C>T​(p.Thr412Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000921 in 1,086,186 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: 9.2e-7 (0 hom. 0 hem.)
• Consequence: PRICKLE3 NM_006150.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.834

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 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=0.11394411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE3	NM_006150.5	c.1235C>T	p.Thr412Ile	missense_variant	8/9	ENST00000599218.6
PRICKLE3	NM_001307979.2	c.1031C>T	p.Thr344Ile	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE3	ENST00000599218.6	c.1235C>T	p.Thr412Ile	missense_variant	8/9	1	NM_006150.5	P3
PRICKLE3	ENST00000453382.5	c.1031C>T	p.Thr344Ile	missense_variant	7/8	5		A2
PRICKLE3	ENST00000540849.5	c.*697C>T		3_prime_UTR_variant, NMD_transcript_variant	7/8	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.21e-7 AC: 1 AN: 1086186 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 354990

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000220

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

Dec 08, 2023

The c.1235C>T (p.T412I) 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 1235, causing the threonine (T) at amino acid position 412 to be replaced by an isoleucine (I). 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	0.084
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.039	T;.
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.97	L;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.76	T
Sift4G	Benign	0.19	T;T
Polyphen		0.14	B;.
Vest4		0.081
MutPred		0.29		Loss of loop (P = 0.0022);.;
MVP		0.22
ClinPred		0.14	T
GERP RS		4.4
Varity_R		0.097
gMVP		0.32

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-49033272;