Variant 19-54123836-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_015629.4(PRPF31):c.615C>G(p.Tyr205*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,634 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRPF31
NM_015629.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: -0.246

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 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 19-54123836-C-G is Pathogenic according to our data. Variant chr19-54123836-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 143149.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-54123836-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4 linkuse as main transcript	c.615C>G	p.Tyr205*	stop_gained	7/14	ENST00000321030.9	NP_056444.3	Q8WWY3-1
PRPF31	XM_006723137.5 linkuse as main transcript	c.615C>G	p.Tyr205*	stop_gained	7/14		XP_006723200.1	Q8WWY3-1
PRPF31	XM_047438587.1 linkuse as main transcript	c.615C>G	p.Tyr205*	stop_gained	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.615C>G	p.Tyr205*	stop_gained	7/14	1	NM_015629.4	ENSP00000324122.4		Q8WWY3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727156

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: Pathogenic

Submissions summary: Pathogenic:2

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

Oct 30, 2022

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 143149). This premature translational stop signal has been observed in individual(s) with PRPF31-related conditions (PMID: 25324289). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr205*) in the PRPF31 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRPF31 are known to be pathogenic (PMID: 18317597, 23950152). -

Retinitis pigmentosa

Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Department of Ophthalmology and Visual Sciences Kyoto University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Benign

0.076

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.50

Vest4

0.94

GERP RS

-1.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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