rs34964511

Variant names:

• chr1-150325557-C-T
• rs34964511
• NM_004698.4:c.146-194C>T

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.146-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,110 control chromosomes in the GnomAD database, including 1,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1315 hom., cov: 31)
• Consequence: PRPF3 NM_004698.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• 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=-0.88).
• BP6: Variant 1-150325557-C-T is Benign according to our data. Variant chr1-150325557-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 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.146-194C>T		intron	N/A	NP_004689.1	O43395-1
	PRPF3	NM_001350529.1		c.-356-194C>T		intron	N/A	NP_001337458.1
	PRPF3	NR_146766.1		n.319-194C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF3	ENST00000324862.7	TSL:1 MANE Select	c.146-194C>T		intron	N/A	ENSP00000315379.6	O43395-1
	PRPF3	ENST00000496202.5	TSL:1	n.308-194C>T		intron	N/A
	PRPF3	ENST00000907626.1		c.146-194C>T		intron	N/A	ENSP00000577685.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16863 AN: 151992 Hom.: 1309 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.0949

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16899 AN: 152110 Hom.: 1315 Cov.: 31 AF XY: 0.106 AC XY: 7911 AN XY: 74354

African (AFR) AF: 0.199 AC: 8245 AN: 41450

American (AMR) AF: 0.0554 AC: 847 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0262 AC: 126 AN: 4818

European-Finnish (FIN) AF: 0.0911 AC: 964 AN: 10586

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0934 AC: 6355 AN: 68014

Other (OTH) AF: 0.0935 AC: 197 AN: 2108

Alfa AF: 0.109 Hom.: 127

Bravo AF: 0.112

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.88
CADD	Benign	3.2
DANN	Benign	0.58
PhyloP100		-0.27
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: rs34964511; hg19: chr1-150298015;