NM_004698.4:c.-48-108T>A

Variant names:

• chr1-150324787-T-A
• rs60758881
• NM_004698.4:c.-48-108T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004698.4(PRPF3):​c.-48-108T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 622,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: PRPF3 NM_004698.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.-48-108T>A		intron	N/A	NP_004689.1	O43395-1
	PRPF3	NM_001350529.1		c.-549-108T>A		intron	N/A	NP_001337458.1
	PRPF3	NR_146766.1		n.126-108T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF3	ENST00000324862.7	TSL:1 MANE Select	c.-48-108T>A		intron	N/A	ENSP00000315379.6	O43395-1
	PRPF3	ENST00000496202.5	TSL:1	n.115-108T>A		intron	N/A
	PRPF3	ENST00000907626.1		c.-48-108T>A		intron	N/A	ENSP00000577685.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000161 AC: 1 AN: 622400 Hom.: 0 AF XY: 0.00000305 AC XY: 1 AN XY: 328206

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15228

American (AMR) AF: 0.0000432 AC: 1 AN: 23142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14848

East Asian (EAS) AF: 0.00 AC: 0 AN: 28648

South Asian (SAS) AF: 0.00 AC: 0 AN: 56160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2032

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 424194

Other (OTH) AF: 0.00 AC: 0 AN: 29334

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		-0.35

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

Other links and lift over

dbSNP: rs60758881; hg19: chr1-150297241;