6-4052069-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003913.5(PRP4K):​c.2287C>T​(p.Leu763Phe) variant causes a missense change. 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 (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRP4K
NM_003913.5 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87
Variant links:
Genes affected
PRP4K (HGNC:17346): (pre-mRNA processing factor kinase PRP4K) Pre-mRNA splicing occurs in two sequential transesterification steps, and the protein encoded by this gene is thought to be involved in pre-mRNA splicing and in signal transduction. This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs). [provided by RefSeq, Jul 2008]
FAM217A (HGNC:21362): (family with sequence similarity 217 member A)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRP4KNM_003913.5 linkc.2287C>T p.Leu763Phe missense_variant Exon 10 of 15 ENST00000337659.11 NP_003904.3 Q13523A0A024QZY5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRPF4BENST00000337659.11 linkc.2287C>T p.Leu763Phe missense_variant Exon 10 of 15 1 NM_003913.5 ENSP00000337194.6 Q13523

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2287C>T (p.L763F) alteration is located in exon 10 (coding exon 10) of the PRPF4B gene. This alteration results from a C to T substitution at nucleotide position 2287, causing the leucine (L) at amino acid position 763 to be replaced by a phenylalanine (F). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.070
D
MetaRNN
Pathogenic
0.75
D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Benign
2.0
M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-3.5
D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0050
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.71
MutPred
0.61
Gain of methylation at K760 (P = 0.1013);
MVP
0.79
MPC
1.6
ClinPred
0.90
D
GERP RS
5.1
Varity_R
0.61
gMVP
0.84

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: chr6-4052303; API