chr19-54124637-T-TCGTG

Variant names:

• chr19-54124637-T-TCGTG
• rs1555793207
• NM_015629.4:c.838_841dupGTGC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_015629.4(PRPF31):​c.838_841dupGTGC​(p.Gln281ArgfsTer44) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRPF31 NM_015629.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.981
• Publications: 1 publications found

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

Our verdict: Pathogenic. The variant received 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 19-54124637-T-TCGTG is Pathogenic according to our data. Variant chr19-54124637-T-TCGTG is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 438046.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	NM_015629.4	MANE Select	c.838_841dupGTGC	p.Gln281ArgfsTer44	frameshift	Exon 8 of 14	NP_056444.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.838_841dupGTGC	p.Gln281ArgfsTer44	frameshift	Exon 8 of 14	ENSP00000324122.4
	PRPF31	ENST00000391755.1	TSL:5	c.838_841dupGTGC	p.Gln281ArgfsTer38	frameshift	Exon 7 of 13	ENSP00000375635.1
	PRPF31	ENST00000419967.5	TSL:5	c.838_841dupGTGC	p.Gln281ArgfsTer44	frameshift	Exon 8 of 13	ENSP00000405166.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa Pathogenic:1

Jan 01, 2015

NIHR Bioresource Rare Diseases, University of Cambridge

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.98
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555793207; hg19: chr19-54628016;