6-41783574-C-T

Variant names:

• chr6-41783574-C-T
• rs530369550
• ENST00000359201.6:c.-545C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000359201.6(PRICKLE4):​c.-545C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PRICKLE4 ENST00000359201.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0590
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03622213).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359201.6. 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.101C>T	p.Pro34Leu	missense	Exon 3 of 8	NP_037529.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE4	ENST00000359201.6	TSL:1	c.-545C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000352128.6	Q2TBC4-1
	PRICKLE4	ENST00000458694.6	TSL:5 MANE Select	c.101C>T	p.Pro34Leu	missense	Exon 3 of 8	ENSP00000404911.1	Q2TBC4-3
	PRICKLE4	ENST00000359201.6	TSL:1	c.-545C>T		5_prime_UTR	Exon 2 of 6	ENSP00000352128.6	Q2TBC4-1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250524 AF XY: 0.0000369

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461552 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 727046

African (AFR) AF: 0.000179 AC: 6 AN: 33472

American (AMR) AF: 0.0000895 AC: 4 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86196

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111834

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74358

African (AFR) AF: 0.000169 AC: 7 AN: 41484

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000508 Hom.: 0

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.4
DANN	Benign	0.62
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.059
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.025
Sift	Benign	0.28	T
Sift4G	Benign	0.76	T
Polyphen		0.022	B
Vest4		0.12
MVP		0.16
MPC		0.39
ClinPred		0.20	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.13
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs530369550; hg19: chr6-41751312; COSMIC: COSV59257689; COSMIC: COSV59257689;