rs11205362

chr1-150325734-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004698.4(PRPF3):c.146-17G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,609,420 control chromosomes in the GnomAD database, including 9,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (678 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9082 hom.)
• Consequence: PRPF3 NM_004698.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.404

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-150325734-G-A is Benign according to our data. Variant chr1-150325734-G-A is described in ClinVar as [Benign]. Clinvar id is 1165123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF3	NM_004698.4	c.146-17G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000324862.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF3	ENST00000324862.7	c.146-17G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004698.4	P1
PRPF3	ENST00000496202.5	n.308-17G>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12449 AN: 151974 Hom.: 678 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0675

GnomAD3 exomes AF: 0.0839 AC: 21101 AN: 251456 Hom.: 1166 AF XY: 0.0842 AC XY: 11444 AN XY: 135910

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.0922

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0327

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.0963

GnomAD4 exome AF: 0.106 AC: 154364 AN: 1457328 Hom.: 9082 Cov.: 32 AF XY: 0.104 AC XY: 75563 AN XY: 725126

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.0478

Gnomad4 ASJ exome AF: 0.0976

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.0327

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.0990

GnomAD4 genome AF: 0.0818 AC: 12445 AN: 152092 Hom.: 678 Cov.: 32 AF XY: 0.0810 AC XY: 6026 AN XY: 74356

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.0675

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.110 Hom.: 763

Bravo AF: 0.0726

Asia WGS AF: 0.0180 AC: 66 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	11
Dann	Benign	0.53

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: rs11205362; hg19: chr1-150298192;