rs144738703

Positions:

• chr19-54123836-C-A
• chr19-54123836-C-G
• chr19-54123836-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_015629.4(PRPF31):​c.615C>A​(p.Tyr205Ter) variant causes a stop gained change involving the alteration of a non-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 (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRPF31 NM_015629.4 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.246

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-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

ACMG classification

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-A is Pathogenic according to our data. Variant chr19-54123836-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 95735.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF31	NM_015629.4	c.615C>A	p.Tyr205Ter	stop_gained	7/14	ENST00000321030.9
PRPF31-AS1	XR_007067340.1	n.88-246G>T		intron_variant, non_coding_transcript_variant
PRPF31	XM_006723137.5	c.615C>A	p.Tyr205Ter	stop_gained	7/14
PRPF31	XM_047438587.1	c.615C>A	p.Tyr205Ter	stop_gained	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF31	ENST00000321030.9	c.615C>A	p.Tyr205Ter	stop_gained	7/14	1	NM_015629.4	P1
PRPF31-AS1	ENST00000452097.1	n.1508G>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 30, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Benign	0.076
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.48	N
MutationTaster	Benign	1.0	A;A;A
Vest4		0.94
GERP RS		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs144738703; hg19: chr19-54627215;