Variant chr19-54123867-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 6P and 4B. PM1PP2PP3_ModeratePP5BS2

The NM_015629.4(PRPF31):c.646G>A(p.Ala216Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,640 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: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PRPF31
NM_015629.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.86

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 Uncertain_significance. Variant got 2 ACMG points.

PM1

In a domain Nop (size 118) in uniprot entity PRP31_HUMAN there are 20 pathogenic changes around while only 0 benign (100%) in NM_015629.4

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PRPF31. . Gene score misZ 3.0492 (greater than the threshold 3.09). Trascript score misZ 3.3753 (greater than threshold 3.09). GenCC has associacion of gene with retinitis pigmentosa 11, PRPF31-related retinopathy, retinitis pigmentosa.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.922

PP5

Variant 19-54123867-G-A is Pathogenic according to our data. Variant chr19-54123867-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3248916.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4 linkuse as main transcript	c.646G>A	p.Ala216Thr	missense_variant	7/14	ENST00000321030.9	NP_056444.3	Q8WWY3-1
PRPF31	XM_006723137.5 linkuse as main transcript	c.646G>A	p.Ala216Thr	missense_variant	7/14		XP_006723200.1	Q8WWY3-1
PRPF31	XM_047438587.1 linkuse as main transcript	c.646G>A	p.Ala216Thr	missense_variant	7/10		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9 linkuse as main transcript	c.646G>A	p.Ala216Thr	missense_variant	7/14	1	NM_015629.4	ENSP00000324122.4		Q8WWY3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251258

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727128

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Retinal dystrophy

Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

.;D;T;.;T;.

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;.;D;D;D;D

M_CAP

Pathogenic

0.60

MetaRNN

Pathogenic

0.92

D;D;D;D;D;D

MetaSVM

Pathogenic

0.80

MutationAssessor

Pathogenic

3.9

H;H;.;.;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.9

D;D;D;D;D;D

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

1.0

.;D;.;.;.;.

Vest4

0.92

MVP

0.75

MPC

1.9

ClinPred

1.0

GERP RS

5.0

Varity_R

0.86

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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