rs587776591

Variant names:

• chr19-54130024-C-G
• rs587776591
• NM_015629.4:c.1374+654C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-54130024-C-G
• chr19-54130024-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_015629.4(PRPF31):​c.1374+654C>G variant causes a intron 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 Pathogenic (★).

• Frequency: Genomes: not found (cov: 28)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: -0.373
• Publications: 5 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 Gene-Disease associations (from GenCC):

• PRPF31-related retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 11

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 19-54130024-C-G is Pathogenic according to our data. Variant chr19-54130024-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 4366.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.1374+654C>G		intron_variant	Intron 13 of 13	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.1374+654C>G		intron_variant	Intron 13 of 13		XP_006723200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.1374+654C>G		intron_variant	Intron 13 of 13	1	NM_015629.4	ENSP00000324122.4
PRPF31	ENST00000391755.1	c.1356+654C>G		intron_variant	Intron 12 of 12	5		ENSP00000375635.1
PRPF31	ENST00000419967.5	c.1460+654C>G		intron_variant	Intron 12 of 12	5		ENSP00000405166.2
PRPF31	ENST00000466404.5	n.1434+654C>G		intron_variant	Intron 10 of 10	2

Frequencies

GnomAD3 genomes Cov.: 28

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 28

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa 11 Pathogenic:1

Sep 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Pathogenic:1

Dec 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	23
DANN	Benign	0.68
PhyloP100		-0.37
Mutation Taster		=100/0	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		3.0
SpliceAI score (max)		0.83		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.83		Position offset: -1

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

Other links and lift over

dbSNP: rs587776591; hg19: chr19-54633455;