chr1-150324880-C-CT

Variant names:

• chr1-150324880-C-CT
• rs75011188
• NM_004698.4:c.-48-3dupT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BS1 BS2

The NM_004698.4(PRPF3):​c.-48-3dupT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,294,178 control chromosomes in the GnomAD database, including 388 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00023 (1 hom., cov: 0)
  • Exomes 𝑓: 0.021 (387 hom.)
• Consequence: PRPF3 NM_004698.4 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713

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 Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.09405458 fraction of the gene. Cryptic splice site detected, with MaxEntScore 13, offset of 0 (no position change), new splice context is: gtctctttttttttttttAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0209 (24093/1150034) while in subpopulation EAS AF= 0.0291 (907/31216). AF 95% confidence interval is 0.0275. There are 387 homozygotes in gnomad4_exome. There are 12167 alleles in male gnomad4_exome subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF3	NM_004698.4	c.-48-3dupT		splice_acceptor_variant, intron_variant	Intron 1 of 15	ENST00000324862.7	NP_004689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF3	ENST00000324862.7	c.-48-15_-48-14insT		intron_variant	Intron 1 of 15	1	NM_004698.4	ENSP00000315379.6
PRPF3	ENST00000496202.5	n.115-15_115-14insT		intron_variant	Intron 1 of 7	1

Frequencies

GnomAD3 genomes AF: 0.000229 AC: 33 AN: 144144 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000209

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00239

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000120

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0209 AC: 24093 AN: 1150034 Hom.: 387 Cov.: 24 AF XY: 0.0211 AC XY: 12167 AN XY: 577414

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.0215

Gnomad4 ASJ exome AF: 0.0292

Gnomad4 EAS exome AF: 0.0291

Gnomad4 SAS exome AF: 0.0186

Gnomad4 FIN exome AF: 0.0269

Gnomad4 NFE exome AF: 0.0204

Gnomad4 OTH exome AF: 0.0235

GnomAD4 genome AF: 0.000229 AC: 33 AN: 144144 Hom.: 1 Cov.: 0 AF XY: 0.000259 AC XY: 18 AN XY: 69598

Gnomad4 AFR AF: 0.0000512

Gnomad4 AMR AF: 0.000209

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00239

Gnomad4 NFE AF: 0.000120

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs75011188; hg19: chr1-150297334;