chr1-150324880-C-CTTTT

Variant names:

• chr1-150324880-C-CTTTT
• rs75011188
• NM_004698.4:c.-48-6_-48-3dupTTTT

Variant summary

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

The NM_004698.4(PRPF3):​c.-48-6_-48-3dupTTTT 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 0.85 (52492 hom., cov: 0)
  • Exomes 𝑓: 0.40 (12452 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 -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: tcttttttttttttttttAGgtg. 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: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.850 AC: 122489 AN: 144162 Hom.: 52489 Cov.: 0

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.851

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.404 AC: 481284 AN: 1190056 Hom.: 12452 Cov.: 24 AF XY: 0.402 AC XY: 240582 AN XY: 597912

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.401

GnomAD4 genome AF: 0.850 AC: 122503 AN: 144190 Hom.: 52492 Cov.: 0 AF XY: 0.849 AC XY: 59119 AN XY: 69656

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.852

Alfa AF: 0.847 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;