1-150324787-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004698.4(PRPF3):c.-48-108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 774,414 control chromosomes in the GnomAD database, including 1,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (432 hom., cov: 31)
  • Exomes 𝑓: 0.015 (634 hom.)
• Consequence: PRPF3 NM_004698.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.349

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-150324787-T-C is Benign according to our data. Variant chr1-150324787-T-C is described in ClinVar as [Benign]. Clinvar id is 1266369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF3	NM_004698.4	c.-48-108T>C		intron_variant		ENST00000324862.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF3	ENST00000324862.7	c.-48-108T>C		intron_variant		1	NM_004698.4	P1
PRPF3	ENST00000496202.5	n.115-108T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7191 AN: 152000 Hom.: 428 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0360

GnomAD4 exome AF: 0.0146 AC: 9086 AN: 622296 Hom.: 634 AF XY: 0.0130 AC XY: 4280 AN XY: 328166

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.00788

Gnomad4 EAS exome AF: 0.0942

Gnomad4 SAS exome AF: 0.00365

Gnomad4 FIN exome AF: 0.0000694

Gnomad4 NFE exome AF: 0.000658

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0474 AC: 7208 AN: 152118 Hom.: 432 Cov.: 31 AF XY: 0.0479 AC XY: 3561 AN XY: 74362

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0823

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.0604

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.0356

Alfa AF: 0.0300 Hom.: 46

Bravo AF: 0.0608

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.6
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60758881; hg19: chr1-150297241;