rs59977379

Variant names:

• chr19-54122085-A-G
• rs59977379
• NM_015629.4:c.322+142A>G

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 2 publications found

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:40700): (PRPF31 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015629.4. 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
	PRPF31	NM_015629.4	MANE Select	c.322+142A>G		intron	N/A	NP_056444.3
	PRPF31-AS1	NR_186329.1		n.473T>C		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.322+142A>G		intron	N/A	ENSP00000324122.4
	PRPF31	ENST00000951323.1		c.322+142A>G		intron	N/A	ENSP00000621382.1
	PRPF31	ENST00000861422.1		c.415+142A>G		intron	N/A	ENSP00000531481.1

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

African (AFR) AF: 0.0413 AC: 802 AN: 19408

American (AMR) AF: 0.0264 AC: 915 AN: 34636

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 1490 AN: 20892

East Asian (EAS) AF: 0.0120 AC: 393 AN: 32736

South Asian (SAS) AF: 0.0457 AC: 3026 AN: 66166

European-Finnish (FIN) AF: 0.0733 AC: 2487 AN: 33952

Middle Eastern (MID) AF: 0.0289 AC: 107 AN: 3704

European-Non Finnish (NFE) AF: 0.0622 AC: 31116 AN: 500372

Other (OTH) AF: 0.0521 AC: 1927 AN: 36998

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

African (AFR) AF: 0.0400 AC: 1664 AN: 41562

American (AMR) AF: 0.0373 AC: 570 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3470

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5172

South Asian (SAS) AF: 0.0438 AC: 211 AN: 4822

European-Finnish (FIN) AF: 0.0772 AC: 818 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4221 AN: 68026

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.71
DANN	Benign	0.26
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs59977379; hg19: chr19-54625464;