NM_006150.5:c.609C>A

Variant names:

• chrX-49178431-G-T
• rs1057519388
• NM_006150.5:c.609C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006150.5(PRICKLE3):​c.609C>A​(p.Ser203Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: PRICKLE3 NM_006150.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.0390
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006150.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE3	NM_006150.5	MANE Select	c.609C>A	p.Ser203Arg	missense	Exon 6 of 9	NP_006141.2
	PRICKLE3	NM_001307979.2		c.405C>A	p.Ser135Arg	missense	Exon 6 of 9	NP_001294908.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE3	ENST00000599218.6	TSL:1 MANE Select	c.609C>A	p.Ser203Arg	missense	Exon 6 of 9	ENSP00000470248.1
	PRICKLE3	ENST00000453382.5	TSL:5	c.405C>A	p.Ser135Arg	missense	Exon 5 of 8	ENSP00000388599.2
	PRICKLE3	ENST00000432913.5	TSL:5	c.405C>A	p.Ser135Arg	missense	Exon 6 of 7	ENSP00000390620.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Progressive sensorineural hearing impairment (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.039
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.7	D
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.67	P
Vest4		0.72
MutPred		0.57		Loss of glycosylation at S203 (P = 0.0094)
MVP		0.42
ClinPred		0.99	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.77
gMVP		0.79
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1057519388; hg19: chrX-49034780;