PRPF6 p.Arg729Arg

Variant names:

• chr20-64027137-G-G
• ENST00000266079.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr20-64027138--
• chr20-64027140-G-T
• chr20-64027140-G-C
• chr20-64027140-G-A
• chr20-64027138-C-A
• chr20-64027138-CGG-AGA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012469.4(PRPF6):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPF6 NM_012469.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 0 publications found

Genes affected

PRPF6 (HGNC:15860): (pre-mRNA processing factor 6) The protein encoded by this gene appears to be involved in pre-mRNA splicing, possibly acting as a bridging factor between U5 and U4/U6 snRNPs in formation of the spliceosome. The encoded protein also can bind androgen receptor, providing a link between transcriptional activation and splicing. [provided by RefSeq, Jul 2008]

PRPF6 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 60

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012469.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF6	NM_012469.4	MANE Select	c.		intron	N/A	NP_036601.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF6	ENST00000266079.5	TSL:1 MANE Select	c.		exon_region	Exon 16 of 21	ENSP00000266079.4	O94906-1
	PRPF6	ENST00000961103.1		c.		exon_region	Exon 17 of 22	ENSP00000631162.1
	PRPF6	ENST00000855544.1		c.		exon_region	Exon 17 of 22	ENSP00000525603.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-62658490;