Variant chr19-54118281-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate

The NM_015629.4(PRPF31):c.3G>C(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRPF31
NM_015629.4 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 8.59

Variant links:

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 links:

PRPF31-AS1 (HGNC:):

PRPF31-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 14 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PS1

Another start lost variant in NM_015629.4 (PRPF31) was described as [Likely_pathogenic] in ClinVar as 438044

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 19-54118281-G-C is Pathogenic according to our data. Variant chr19-54118281-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 2818311.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRPF31	NM_015629.4 linkuse as main transcript	c.3G>C	p.Met1?	start_lost	2/14	ENST00000321030.9
PRPF31-AS1	XR_007067340.1 linkuse as main transcript	n.1843-602C>G		intron_variant, non_coding_transcript_variant
PRPF31	XM_006723137.5 linkuse as main transcript	c.3G>C	p.Met1?	start_lost	2/14
PRPF31	XM_047438587.1 linkuse as main transcript	c.3G>C	p.Met1?	start_lost	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF31	ENST00000321030.9 linkuse as main transcript	c.3G>C	p.Met1?	start_lost	2/14	1	NM_015629.4	P1	Q8WWY3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 03, 2022

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Disruption of the initiator codon has been observed in individuals with retinitis pigmentosa (PMID: 28041643; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the PRPF31 mRNA. The next in-frame methionine is located at codon 59. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.65

.;D;T;.;T;.

Eigen

Benign

0.026

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;.;D;D;D;D

M_CAP

Pathogenic

0.93

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D

MetaSVM

Uncertain

0.14

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Uncertain

-3.4

D;D;D;D;D;D

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.0

.;B;.;.;.;.

Vest4

0.92

MutPred

0.96

Gain of catalytic residue at M1 (P = 0.0276);Gain of catalytic residue at M1 (P = 0.0276);Gain of catalytic residue at M1 (P = 0.0276);Gain of catalytic residue at M1 (P = 0.0276);Gain of catalytic residue at M1 (P = 0.0276);Gain of catalytic residue at M1 (P = 0.0276);

MVP

0.97

ClinPred

0.99

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.82

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 11

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over