chr19-54122530-CA-C
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015629.4(PRPF31):c.359del(p.Lys120ArgfsTer78) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). 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 frameshift
NM_015629.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.987
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 19-54122530-CA-C is Pathogenic according to our data. Variant chr19-54122530-CA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438045.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-54122530-CA-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPF31 | NM_015629.4 | c.359del | p.Lys120ArgfsTer78 | frameshift_variant | 5/14 | ENST00000321030.9 | |
PRPF31-AS1 | XR_007067340.1 | n.1147del | non_coding_transcript_exon_variant | 2/3 | |||
PRPF31 | XM_006723137.5 | c.359del | p.Lys120ArgfsTer78 | frameshift_variant | 5/14 | ||
PRPF31 | XM_047438587.1 | c.359del | p.Lys120ArgfsTer78 | frameshift_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF31 | ENST00000321030.9 | c.359del | p.Lys120ArgfsTer78 | frameshift_variant | 5/14 | 1 | NM_015629.4 | P1 | |
PRPF31-AS1 | ENST00000452097.1 | n.2813del | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461792Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727216
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
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 | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at