19-54118279-A-G

Position:

• chr19-54118279-A-G

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1 PS1_Moderate PM2 PP5_Moderate

The NM_015629.4(PRPF31):​c.1A>G​(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
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.01

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:):

ACMG classification

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 19-54118279-A-G is Pathogenic according to our data. Variant chr19-54118279-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 3235232.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.1A>G	p.Met1?	start_lost	2/14	ENST00000321030.9
PRPF31-AS1	XR_007067340.1	n.1843-600T>C		intron_variant, non_coding_transcript_variant
PRPF31	XM_006723137.5	c.1A>G	p.Met1?	start_lost	2/14
PRPF31	XM_047438587.1	c.1A>G	p.Met1?	start_lost	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF31	ENST00000321030.9	c.1A>G	p.Met1?	start_lost	2/14	1	NM_015629.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa 11 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

MVZ Medizinische Genetik Mainz

Nov 03, 2021

ACMG Criteria: PVS1, PM5, PM2_SUP, PP4 (ACMG Version 3) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	.;D;T;.;T;.
Eigen	Benign	0.075
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;.;D;D;D;D
M_CAP	Pathogenic	0.95	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D
MetaSVM	Uncertain	0.19	D
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Uncertain	-3.3	D;D;D;D;D;D
REVEL	Pathogenic	0.82
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		0.93
MutPred		0.97		Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);
MVP		0.98
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54621659;