Variant 19-54118279-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP3PP5

The NM_015629.4(PRPF31):c.1A>T(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRPF31
NM_015629.4 start_lost

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.01

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:

Genome browser will be placed here

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 Lovd

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 19-54118279-A-T is Pathogenic according to our data. Variant chr19-54118279-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438044.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-54118279-A-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRPF31	NM_015629.4 linkuse as main transcript	c.1A>T	p.Met1?	start_lost	2/14	ENST00000321030.9	NP_056444.3
PRPF31-AS1	XR_007067340.1 linkuse as main transcript	n.1843-600T>A		intron_variant, non_coding_transcript_variant
PRPF31	XM_006723137.5 linkuse as main transcript	c.1A>T	p.Met1?	start_lost	2/14		XP_006723200.1
PRPF31	XM_047438587.1 linkuse as main transcript	c.1A>T	p.Met1?	start_lost	2/10		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9 linkuse as main transcript	c.1A>T	p.Met1?	start_lost	2/14	1	NM_015629.4	ENSP00000324122	P1	Q8WWY3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460676

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

Jan 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Uncertain

0.51

.;D;T;.;T;.

Eigen

Benign

0.075

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;.;D;D;D;D

M_CAP

Pathogenic

0.94

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D

MetaSVM

Uncertain

0.093

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Uncertain

-2.6

D;D;D;D;D;D

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.0010

.;B;.;.;.;.

Vest4

0.91

MutPred

0.93

Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);

MVP

0.98

ClinPred

0.98

GERP RS

4.8

Varity_R

0.85

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.52

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.52

Position offset: 13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over