1-150324985-A-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_004698.4(PRPF3):c.43A>G(p.Ile15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PRPF3
NM_004698.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

PRPF3 (HGNC:17348): (pre-mRNA processing factor 3) The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. This gene product is one of several proteins that associate with U4 and U6 snRNPs. Mutations in this gene are associated with retinitis pigmentosa-18. [provided by RefSeq, Jul 2008]

PRPF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2

Missense variant where missense usually causes diseases, PRPF3

BP4

Computational evidence support a benign effect (MetaRNN=0.07275608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF3	NM_004698.4 linkuse as main transcript	c.43A>G	p.Ile15Val	missense_variant	2/16	ENST00000324862.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF3	ENST00000324862.7 linkuse as main transcript	c.43A>G	p.Ile15Val	missense_variant	2/16	1	NM_004698.4	P1	O43395-1
PRPF3	ENST00000496202.5 linkuse as main transcript	n.205A>G		non_coding_transcript_exon_variant	2/8	1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151660

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2023

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 15 of the PRPF3 protein (p.Ile15Val). This variant is present in population databases (no rsID available, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with PRPF3-related conditions. ClinVar contains an entry for this variant (Variation ID: 2060845). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Benign

0.64

DEOGEN2

Benign

0.083

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

M_CAP

Benign

0.0037

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.26

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.13

REVEL

Benign

0.059

Sift

Benign

0.54

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.15

MutPred

0.63

Gain of disorder (P = 0.1023);

MVP

0.26

MPC

0.81

ClinPred

0.54

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.056

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over