Variant 20-63981168-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012469.4(PRPF6):c.-78G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 1,467,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

PRPF6
NM_012469.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.470

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:

PRPF6 (HGNC:):

PRPF6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 20-63981168-G-A is Benign according to our data. Variant chr20-63981168-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 339457.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 241 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
PRPF6	NM_012469.4 linkuse as main transcript	c.-78G>A	5_prime_UTR_variant	1/21	ENST00000266079.5	NP_036601.2	O94906-1
PRPF6	XM_006723769.4 linkuse as main transcript	c.-78G>A	5_prime_UTR_variant	1/20		XP_006723832.1
PRPF6	XR_007067448.1 linkuse as main transcript	n.37G>A	non_coding_transcript_exon_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF6	ENST00000266079.5 linkuse as main transcript	c.-78G>A		5_prime_UTR_variant	1/21	1	NM_012469.4	ENSP00000266079.4		O94906-1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.000148

AC:

195

AN:

1315454

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

653732

show subpopulations

Gnomad4 AFR exome

AF:

0.00548

Gnomad4 AMR exome

AF:

0.000279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000563

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000299

Gnomad4 OTH exome

AF:

0.000253

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152370

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00548

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00200

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.0

DANN

Benign

0.88

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

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