1-150324880-CTTT-CTTTTTTTTTT

Variant names:

• chr1-150324880-C-CTTTTTTT
• rs75011188
• NM_004698.4:c.-48-9_-48-3dupTTTTTTT

Variant summary

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

The NM_004698.4(PRPF3):​c.-48-9_-48-3dupTTTTTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,343,504 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000019 (0 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 -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 14, offset of 0 (no position change), new splice context is: ttttttttttttttttttAGgtg. 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 GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF3	NM_004698.4	c.-48-9_-48-3dupTTTTTTT		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_-48-14insTTTTTTT		intron_variant	Intron 1 of 15	1	NM_004698.4	ENSP00000315379.6
PRPF3	ENST00000496202.5	n.115-15_115-14insTTTTTTT		intron_variant	Intron 1 of 7	1

Frequencies

GnomAD3 genomes AF: 0.0000139 AC: 2 AN: 144204 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000696

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 23 AN: 1199300 Hom.: 0 Cov.: 24 AF XY: 0.0000232 AC XY: 14 AN XY: 602846

Gnomad4 AFR exome AF: 0.0000392

Gnomad4 AMR exome AF: 0.0000954

Gnomad4 ASJ exome AF: 0.0000976

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000545

Gnomad4 FIN exome AF: 0.0000540

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000208

GnomAD4 genome AF: 0.0000139 AC: 2 AN: 144204 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 69632

Gnomad4 AFR AF: 0.0000256

Gnomad4 AMR AF: 0.0000696

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;