Variant chr20-63981322-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012469.4(PRPF6):c.71+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,579,058 control chromosomes in the GnomAD database, including 11,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 781 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10703 hom. )

Consequence

PRPF6
NM_012469.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.001308

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.24

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 20-63981322-G-A is Benign according to our data. Variant chr20-63981322-G-A is described in ClinVar as [Benign]. Clinvar id is 339463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63981322-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PRPF6	NM_012469.4 linkuse as main transcript	c.71+6G>A	splice_donor_region_variant, intron_variant	ENST00000266079.5
PRPF6	XM_006723769.4 linkuse as main transcript	c.71+6G>A	splice_donor_region_variant, intron_variant
PRPF6	XR_007067448.1 linkuse as main transcript	n.185+6G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF6	ENST00000266079.5 linkuse as main transcript	c.71+6G>A		splice_donor_region_variant, intron_variant		1	NM_012469.4	P1	O94906-1

Frequencies

GnomAD3 genomes

AF:

0.0868

AC:

13200

AN:

152158

Hom.:

785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.0831

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0427

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0866

GnomAD3 exomes

AF:

0.123

AC:

23159

AN:

187794

Hom.:

1640

AF XY:

0.132

AC XY:

13476

AN XY:

102058

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.0885

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.0439

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.117

AC:

167197

AN:

1426782

Hom.:

10703

Cov.:

AF XY:

0.121

AC XY:

85369

AN XY:

706524

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.0905

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.0334

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.0867

AC:

13197

AN:

152276

Hom.:

781

Cov.:

AF XY:

0.0904

AC XY:

6729

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0219

Gnomad4 AMR

AF:

0.0832

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.0426

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.0857

Alfa

AF:

0.106

Hom.:

312

Bravo

AF:

0.0779

Asia WGS

AF:

0.154

AC:

535

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over