1-150324779-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.16

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]

ACMG classification

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/exons	MANE	UniProt
PRPF3	NM_004698.4	c.-48-116C>A		intron_variant		ENST00000324862.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF3	ENST00000324862.7	c.-48-116C>A		intron_variant		1	NM_004698.4	P1
PRPF3	ENST00000496202.5	n.115-116C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0770 AC: 11690 AN: 151904 Hom.: 565 Cov.: 31

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

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.: 31 AF XY: 0.0740 AC XY: 5501 AN XY: 74308

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.: 68

Bravo AF: 0.0742

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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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

Other links and lift over

dbSNP: rs35437473; hg19: chr1-150297233;