rs59977379

Positions:

• chr19-54122085-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015629.4(PRPF31):​c.322+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 901,110 control chromosomes in the GnomAD database, including 1,580 homozygotes. 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: 𝑓 0.052 (225 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1355 hom.)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

Genes affected

PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]

PRPF31-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.322+142A>G		intron_variant		ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.322+142A>G		intron_variant			XP_006723200.1
PRPF31	XM_047438587.1	c.322+142A>G		intron_variant			XP_047294543.1
PRPF31-AS1	NR_186329.1	n.473T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.322+142A>G		intron_variant		1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7929 AN: 152128 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0564 AC: 42263 AN: 748864 Hom.: 1355 Cov.: 10 AF XY: 0.0562 AC XY: 21910 AN XY: 389716

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.0264

Gnomad4 ASJ exome AF: 0.0713

Gnomad4 EAS exome AF: 0.0120

Gnomad4 SAS exome AF: 0.0457

Gnomad4 FIN exome AF: 0.0733

Gnomad4 NFE exome AF: 0.0622

Gnomad4 OTH exome AF: 0.0521

GnomAD4 genome AF: 0.0522 AC: 7941 AN: 152246 Hom.: 225 Cov.: 32 AF XY: 0.0521 AC XY: 3874 AN XY: 74420

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0438

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0595 Hom.: 63

Bravo AF: 0.0477

Asia WGS AF: 0.0300 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.71
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs59977379; hg19: chr19-54625464;