rs138184463

Variant names:

• chr6-41783523-C-A
• NM_013397.6:c.50C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-41783523-C-A
• chr6-41783523-C-T

Variant summary

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

The NM_013397.6(PRICKLE4):​c.50C>A​(p.Pro17His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRICKLE4 NM_013397.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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

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=0.12295088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE4	NM_013397.6	c.50C>A	p.Pro17His	missense_variant	Exon 3 of 8	ENST00000458694.6	NP_037529.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE4	ENST00000458694.6	c.50C>A	p.Pro17His	missense_variant	Exon 3 of 8	5	NM_013397.6	ENSP00000404911.1
ENSG00000124593	ENST00000335515.10	n.50C>A		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000335185.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447710 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.6
DANN	Uncertain	0.99
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.34	T;.
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.92	P;P
Vest4		0.098
MutPred		0.32		Loss of catalytic residue at P17 (P = 0.057);Loss of catalytic residue at P17 (P = 0.057);
MVP		0.34
MPC		0.94
ClinPred		0.64	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-41751261;