Genetic Variant PRPF6:c.-25C>T (chr20-63981221-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012469.4(PRPF6):c.-25C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,592,058 control chromosomes in the GnomAD database, including 2,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 129 hom., cov: 33)

Exomes 𝑓: 0.048 ( 1911 hom. )

Consequence

PRPF6
NM_012469.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.143

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa 60
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRPF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 20-63981221-C-T is Benign according to our data. Variant chr20-63981221-C-T is described in ClinVar as Benign. ClinVar VariationId is 339460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

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.-25C>T		5_prime_UTR	Exon 1 of 21	NP_036601.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPF6	ENST00000266079.5	TSL:1 MANE Select	c.-25C>T	5_prime_UTR	Exon 1 of 21	ENSP00000266079.4	O94906-1
PRPF6	ENST00000961103.1		c.-25C>T	5_prime_UTR	Exon 1 of 22	ENSP00000631162.1
PRPF6	ENST00000855544.1		c.-25C>T	5_prime_UTR	Exon 1 of 22	ENSP00000525603.1

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4856

AN:

152250

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00859

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0211

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0534

Gnomad OTH

AF:

0.0296

GnomAD2 exomes

AF:

0.0317

AC:

6777

AN:

213972

AF XY:

0.0330

show subpopulations

Gnomad AFR exome

AF:

0.00825

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.0000617

Gnomad FIN exome

AF:

0.0286

Gnomad NFE exome

AF:

0.0500

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0478

AC:

68881

AN:

1439690

Hom.:

1911

Cov.:

AF XY:

0.0475

AC XY:

33927

AN XY:

714150

show subpopulations

African (AFR)

AF:

0.00649

AC:

215

AN:

33104

American (AMR)

AF:

0.0148

AC:

618

AN:

41706

Ashkenazi Jewish (ASJ)

AF:

0.0244

AC:

626

AN:

25624

East Asian (EAS)

AF:

0.000154

AC:

AN:

38846

South Asian (SAS)

AF:

0.0233

AC:

1941

AN:

83166

European-Finnish (FIN)

AF:

0.0316

AC:

1622

AN:

51268

Middle Eastern (MID)

AF:

0.0313

AC:

180

AN:

5742

European-Non Finnish (NFE)

AF:

0.0555

AC:

61094

AN:

1100714

Other (OTH)

AF:

0.0433

AC:

2579

AN:

59520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3445

6890

10335

13780

17225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2200

4400

6600

8800

11000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0319

AC:

4855

AN:

152368

Hom.:

129

Cov.:

AF XY:

0.0303

AC XY:

2256

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00856

AC:

356

AN:

41586

American (AMR)

AF:

0.0210

AC:

322

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.0184

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0254

AC:

270

AN:

10628

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0534

AC:

3636

AN:

68032

Other (OTH)

AF:

0.0293

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

248

497

745

994

1242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0471

Hom.:

Bravo

AF:

0.0311

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.7

(source)

DANN

Benign

0.94

PhyloP100

-0.14

PromoterAI

-0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=295/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over