1-150324880-CTTT-CTTTTTTTT

Variant names:

• chr1-150324880-C-CTTTTT
• rs75011188
• NM_004698.4:c.-48-7_-48-3dupTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_Moderate BS2

The NM_004698.4(PRPF3):​c.-48-7_-48-3dupTTTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 0)
  • Exomes 𝑓: 0.010 (144 hom.)
  • Failed GnomAD Quality Control
• 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 -2 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: ctttttttttttttttttAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BS2: High AC in GnomAd4 at 381 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 372 AN: 144180 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00540

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00160

Gnomad ASJ AF: 0.000584

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00202

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0104 AC: 12460 AN: 1195494 Hom.: 144 Cov.: 24 AF XY: 0.0103 AC XY: 6188 AN XY: 600808

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.0104

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.00987

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.00264 AC: 381 AN: 144208 Hom.: 3 Cov.: 0 AF XY: 0.00264 AC XY: 184 AN XY: 69662

Gnomad4 AFR AF: 0.00560

Gnomad4 AMR AF: 0.00160

Gnomad4 ASJ AF: 0.000584

Gnomad4 EAS AF: 0.00159

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.00251

Alfa AF: 0.00134 Hom.: 1622

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;