NM_004698.4:c.-48-116C>A

Variant names:

• chr1-150324779-C-A
• rs35437473
• NM_004698.4:c.-48-116C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 18

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004698.4. 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
	PRPF3	NM_004698.4	MANE Select	c.-48-116C>A		intron	N/A	NP_004689.1	O43395-1
	PRPF3	NM_001350529.1		c.-549-116C>A		intron	N/A	NP_001337458.1
	PRPF3	NR_146766.1		n.126-116C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF3	ENST00000324862.7	TSL:1 MANE Select	c.-48-116C>A		intron	N/A	ENSP00000315379.6	O43395-1
	PRPF3	ENST00000496202.5	TSL:1	n.115-116C>A		intron	N/A
	PRPF3	ENST00000907626.1		c.-48-116C>A		intron	N/A	ENSP00000577685.1

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

African (AFR) AF: 0.0760 AC: 1058 AN: 13916

American (AMR) AF: 0.0337 AC: 707 AN: 20964

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 332 AN: 13538

East Asian (EAS) AF: 0.0000371 AC: 1 AN: 26982

South Asian (SAS) AF: 0.0314 AC: 1674 AN: 53292

European-Finnish (FIN) AF: 0.0899 AC: 2343 AN: 26050

Middle Eastern (MID) AF: 0.0585 AC: 111 AN: 1898

European-Non Finnish (NFE) AF: 0.0951 AC: 35125 AN: 369304

Other (OTH) AF: 0.0674 AC: 1795 AN: 26634

GnomAD4 genome AF: 0.0770 AC: 11707 AN: 152022 Hom.: 566 Cov.: 31 AF XY: 0.0740 AC XY: 5501 AN XY: 74308

African (AFR) AF: 0.0809 AC: 3356 AN: 41472

American (AMR) AF: 0.0430 AC: 656 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0254 AC: 122 AN: 4812

European-Finnish (FIN) AF: 0.0913 AC: 962 AN: 10534

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6304 AN: 67980

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0877 Hom.: 71

Bravo AF: 0.0742

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.22
DANN	Benign	0.25
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35437473; hg19: chr1-150297233;