1-150324880-CTTT-CTTTTTT

Variant names:

• chr1-150324880-C-CTTT
• rs75011188
• NM_004698.4:c.-48-5_-48-3dupTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_Moderate BP6_Moderate BA1

The NM_004698.4(PRPF3):​c.-48-5_-48-3dupTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1901 hom., cov: 0)
  • Exomes 𝑓: 0.36 (9793 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRPF3 NM_004698.4 splice_acceptor, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -8 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: ctctttttttttttttttAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BP6: Variant 1-150324880-C-CTTT is Benign according to our data. Variant chr1-150324880-C-CTTT is described in ClinVar as [Benign]. Clinvar id is 1178706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.144 AC: 20814 AN: 144042 Hom.: 1900 Cov.: 0

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.143

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.357 AC: 419749 AN: 1176664 Hom.: 9793 Cov.: 24 AF XY: 0.356 AC XY: 210468 AN XY: 591106

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.362

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.145 AC: 20818 AN: 144068 Hom.: 1901 Cov.: 0 AF XY: 0.145 AC XY: 10078 AN XY: 69582

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.142

Alfa AF: 0.152 Hom.: 1622

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 02, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;