NM_013397.6:c.185C>G

Variant names:

• chr6-41784183-C-G
• NM_013397.6:c.185C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013397.6(PRICKLE4):​c.185C>G​(p.Pro62Arg) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRICKLE4 NM_013397.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.612
• Publications: 0 publications found

Genes affected

PRICKLE4 (HGNC:16805): (prickle planar cell polarity protein 4) C6ORF49 is a member of the LIM domain protein family (Teufel et al., 2005 [PubMed 15702247]).[supplied by OMIM, Mar 2008]

ENSG00000124593 (HGNC:):

FRS3 (HGNC:16970): (fibroblast growth factor receptor substrate 3) This gene encodes a substrate for the fibroblast growth factor receptor. The encoded protein is found in the peripheral plasma membrane and links fibroblast growth factor receptor stimulation to activators of Ras. The encoded protein down-regulates extracellular regulated kinase 2 through direct binding. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15377733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013397.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE4	NM_013397.6	MANE Select	c.185C>G	p.Pro62Arg	missense	Exon 4 of 8	NP_037529.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE4	ENST00000458694.6	TSL:5 MANE Select	c.185C>G	p.Pro62Arg	missense	Exon 4 of 8	ENSP00000404911.1	Q2TBC4-3
	PRICKLE4	ENST00000359201.6	TSL:1	c.65C>G	p.Pro22Arg	missense	Exon 2 of 6	ENSP00000352128.6	Q2TBC4-1
	ENSG00000124593	ENST00000335515.10	TSL:2	n.185C>G		non_coding_transcript_exon	Exon 3 of 9	ENSP00000335185.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		0.61
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.099
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.060	T
Polyphen		0.23	B
Vest4		0.38
MutPred		0.67		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.11
MPC		0.51
ClinPred		0.23	T
GERP RS		2.9
PromoterAI		0.0077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.35
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr6-41751921;