Genetic Variant PRPF3:c.-48-116C>A (chr1-150324779-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004698.4(PRPF3):c.-48-116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 704,600 control chromosomes in the GnomAD database, including 2,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.077 ( 566 hom., cov: 31)

Exomes 𝑓: 0.078 ( 1971 hom. )

Consequence

PRPF3
NM_004698.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.16

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 1-150324779-C-A is Benign according to our data. Variant chr1-150324779-C-A is described in ClinVar as [Benign]. Clinvar id is 1224950.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF3	NM_004698.4 link	c.-48-116C>A		intron_variant	Intron 1 of 15	ENST00000324862.7	NP_004689.1	O43395-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF3	ENST00000324862.7 link	c.-48-116C>A		intron_variant	Intron 1 of 15	1	NM_004698.4	ENSP00000315379.6		O43395-1
PRPF3	ENST00000496202.5 link	n.115-116C>A		intron_variant	Intron 1 of 7	1

Frequencies

GnomAD3 genomes

AF:

0.0770

AC:

11690

AN:

151904

Hom.:

565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0431

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0913

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.0713

GnomAD4 exome

AF:

0.0781

AC:

43146

AN:

552578

Hom.:

1971

AF XY:

0.0753

AC XY:

22077

AN XY:

293064

show subpopulations

Gnomad4 AFR exome

AF:

0.0760

Gnomad4 AMR exome

AF:

0.0337

Gnomad4 ASJ exome

AF:

0.0245

Gnomad4 EAS exome

AF:

0.0000371

Gnomad4 SAS exome

AF:

0.0314

Gnomad4 FIN exome

AF:

0.0899

Gnomad4 NFE exome

AF:

0.0951

Gnomad4 OTH exome

AF:

0.0674

GnomAD4 genome

AF:

0.0770

AC:

11707

AN:

152022

Hom.:

566

Cov.:

AF XY:

0.0740

AC XY:

5501

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0809

Gnomad4 AMR

AF:

0.0430

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0254

Gnomad4 FIN

AF:

0.0913

Gnomad4 NFE

AF:

0.0927

Gnomad4 OTH

AF:

0.0701

Alfa

AF:

0.0876

Hom.:

Bravo

AF:

0.0742

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.22

DANN

Benign

0.25

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