1-150324880-CTTT-CTTTTT

Variant names:

• chr1-150324880-C-CTT
• rs75011188
• NM_004698.4:c.-48-4_-48-3dupTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The NM_004698.4(PRPF3):​c.-48-4_-48-3dupTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,251,300 control chromosomes in the GnomAD database, including 2,163 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 0)
  • Exomes 𝑓: 0.13 (2162 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: tctcttttttttttttttAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF3	NM_004698.4	c.-48-4_-48-3dupTT		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_-48-14insTT		intron_variant	Intron 1 of 15	1	NM_004698.4	ENSP00000315379.6
PRPF3	ENST00000496202.5	n.115-15_115-14insTT		intron_variant	Intron 1 of 7	1

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 169 AN: 144028 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000697

Gnomad ASJ AF: 0.000584

Gnomad EAS AF: 0.000792

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00114

Gnomad OTH AF: 0.00354

GnomAD4 exome AF: 0.132 AC: 146676 AN: 1107244 Hom.: 2162 Cov.: 24 AF XY: 0.134 AC XY: 74527 AN XY: 555092

Gnomad4 AFR exome AF: 0.0913

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.00117 AC: 169 AN: 144056 Hom.: 1 Cov.: 0 AF XY: 0.00128 AC XY: 89 AN XY: 69562

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000697

Gnomad4 ASJ AF: 0.000584

Gnomad4 EAS AF: 0.000795

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00681

Gnomad4 NFE AF: 0.00114

Gnomad4 OTH AF: 0.00352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;