20-64019609-G-T

Variant names:

• chr20-64019609-G-T
• rs816922
• NM_012469.4:c.1647+2764G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012469.4(PRPF6):​c.1647+2764G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,242 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (315 hom., cov: 31)
• Consequence: PRPF6 NM_012469.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF6	NM_012469.4	c.1647+2764G>T		intron_variant	Intron 12 of 20	ENST00000266079.5	NP_036601.2
PRPF6	XM_006723769.4	c.1428+2764G>T		intron_variant	Intron 11 of 19		XP_006723832.1
PRPF6	XR_007067448.1	n.1761+2764G>T		intron_variant	Intron 12 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF6	ENST00000266079.5	c.1647+2764G>T		intron_variant	Intron 12 of 20	1	NM_012469.4	ENSP00000266079.4

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9553 AN: 152124 Hom.: 315 Cov.: 31

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0822

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0628 AC: 9556 AN: 152242 Hom.: 315 Cov.: 31 AF XY: 0.0627 AC XY: 4666 AN XY: 74440

African (AFR) AF: 0.0663 AC: 2754 AN: 41560

American (AMR) AF: 0.0809 AC: 1237 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4826

European-Finnish (FIN) AF: 0.0622 AC: 659 AN: 10602

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4294 AN: 67990

Other (OTH) AF: 0.0809 AC: 171 AN: 2114

Alfa AF: 0.0520 Hom.: 166

Bravo AF: 0.0644

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs816922; hg19: chr20-62650962;