NM_004698.4:c.45A>C

Variant names:

• chr1-150324987-A-C
• NM_004698.4:c.45A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004698.4(PRPF3):​c.45A>C​(p.Ile15Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRPF3 NM_004698.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48
• Publications: 0 publications found

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]

PRPF3 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 18

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 1-150324987-A-C is Benign according to our data. Variant chr1-150324987-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3659580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.48 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004698.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF3	NM_004698.4	MANE Select	c.45A>C	p.Ile15Ile	synonymous	Exon 2 of 16	NP_004689.1	O43395-1
	PRPF3	NM_001350529.1		c.-457A>C		5_prime_UTR	Exon 2 of 17	NP_001337458.1
	PRPF3	NR_146766.1		n.218A>C		non_coding_transcript_exon	Exon 2 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF3	ENST00000324862.7	TSL:1 MANE Select	c.45A>C	p.Ile15Ile	synonymous	Exon 2 of 16	ENSP00000315379.6	O43395-1
	PRPF3	ENST00000496202.5	TSL:1	n.207A>C		non_coding_transcript_exon	Exon 2 of 8
	PRPF3	ENST00000907626.1		c.45A>C	p.Ile15Ile	synonymous	Exon 2 of 16	ENSP00000577685.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.7
DANN	Benign	0.74
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=292/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr1-150297445;