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GeneBe

1-150325086-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004698.4(PRPF3):c.144C>T(p.Ala48=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PRPF3
NM_004698.4 splice_region, synonymous

Scores

2
Splicing: ADA: 0.0004899
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-150325086-C-T is Benign according to our data. Variant chr1-150325086-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 956951.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.05 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRPF3NM_004698.4 linkuse as main transcriptc.144C>T p.Ala48= splice_region_variant, synonymous_variant 2/16 ENST00000324862.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRPF3ENST00000324862.7 linkuse as main transcriptc.144C>T p.Ala48= splice_region_variant, synonymous_variant 2/161 NM_004698.4 P1O43395-1
PRPF3ENST00000496202.5 linkuse as main transcriptn.306C>T splice_region_variant, non_coding_transcript_exon_variant 2/81

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000790
AC:
12
AN:
151914
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.000147
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251412
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1461054
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
726838
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000789
AC:
12
AN:
152032
Hom.:
0
Cov.:
31
AF XY:
0.0000942
AC XY:
7
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000453
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeAug 31, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
Cadd
Benign
6.9
Dann
Benign
0.67
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00049
dbscSNV1_RF
Benign
0.044
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370220628; hg19: chr1-150297544; COSMIC: COSV61395880; COSMIC: COSV61395880; API