chr19-54123802-C-A

Variant names:

• chr19-54123802-C-A
• rs119475043
• NM_015629.4:c.581C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1 PM2 PP3_Strong PP5

The NM_015629.4(PRPF31):​c.581C>A​(p.Ala194Glu) variant causes a missense change. 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 (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRPF31 NM_015629.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.96

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 Likely_pathogenic. Variant got 9 ACMG points.

• PM1: In a helix (size 34) in uniprot entity PRP31_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_015629.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98
• PP5: Variant 19-54123802-C-A is Pathogenic according to our data. Variant chr19-54123802-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 4362.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null. Variant chr19-54123802-C-A is described in UniProt as null.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.581C>A	p.Ala194Glu	missense_variant	Exon 7 of 14	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.581C>A	p.Ala194Glu	missense_variant	Exon 7 of 14		XP_006723200.1
PRPF31	XM_047438587.1	c.581C>A	p.Ala194Glu	missense_variant	Exon 7 of 10		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.581C>A	p.Ala194Glu	missense_variant	Exon 7 of 14	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 11 Pathogenic:1

Apr 06, 2007

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	.;D;T;.;T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;.;D;D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.3	M;M;.;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.4	D;D;D;D;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0030	D;D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;.
Vest4		0.97
MutPred		0.94		Gain of disorder (P = 0.0169);Gain of disorder (P = 0.0169);Gain of disorder (P = 0.0169);Gain of disorder (P = 0.0169);Gain of disorder (P = 0.0169);Gain of disorder (P = 0.0169);
MVP		0.84
MPC		2.1
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.97
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs119475043; hg19: chr19-54627181;