NM_004698.4:c.146-194C>T

Variant names:

• chr1-150325557-C-T
• rs34964511
• NM_004698.4:c.146-194C>T

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.146-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,110 control chromosomes in the GnomAD database, including 1,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1315 hom., cov: 31)
• Consequence: PRPF3 NM_004698.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270

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=-0.88).
• BP6: Variant 1-150325557-C-T is Benign according to our data. Variant chr1-150325557-C-T is described in ClinVar as [Benign]. Clinvar id is 1271800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF3	NM_004698.4	c.146-194C>T		intron_variant	Intron 2 of 15	ENST00000324862.7	NP_004689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF3	ENST00000324862.7	c.146-194C>T		intron_variant	Intron 2 of 15	1	NM_004698.4	ENSP00000315379.6
PRPF3	ENST00000496202.5	n.308-194C>T		intron_variant	Intron 2 of 7	1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16863 AN: 151992 Hom.: 1309 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.0949

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16899 AN: 152110 Hom.: 1315 Cov.: 31 AF XY: 0.106 AC XY: 7911 AN XY: 74354

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0262

Gnomad4 FIN AF: 0.0911

Gnomad4 NFE AF: 0.0934

Gnomad4 OTH AF: 0.0935

Alfa AF: 0.106 Hom.: 112

Bravo AF: 0.112

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.58

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: rs34964511; hg19: chr1-150298015;