rs553265417

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 8P and 12B. PVS1BP6_Very_StrongBS2

The NM_203288.2(RP9):c.664delT(p.Ter222AspfsTer29) variant causes a frameshift, stop lost change. The variant allele was found at a frequency of 0.0076 in 152,304 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 103 hom. )

Failed GnomAD Quality Control

Consequence

RP9
NM_203288.2 frameshift, stop_lost

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.31

Publications

5 publications found

Variant links:

Genes affected

RP9 (HGNC:10288): (RP9 pre-mRNA splicing factor) The protein encoded by this gene can be bound and phosphorylated by the protooncogene PIM1 product, a serine/threonine protein kinase . This protein localizes in nuclear speckles containing the splicing factors, and has a role in pre-mRNA splicing. CBF1-interacting protein (CIR), a corepressor of CBF1, can also bind to this protein and effects alternative splicing. Mutations in this gene result in autosomal dominant retinitis pigmentosa-9. This gene has a pseudogene (GeneID: 441212), which is located in tandem array approximately 166 kb distal to this gene. [provided by RefSeq, Sep 2009]

RP9 Gene-Disease associations (from GenCC):

retinitis pigmentosa 9
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RP9 links:

ENSG00000302625 (HGNC:):

ENSG00000302625 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PVS1

Stoplost variant. No alternative stopcodon identified downstream, so we assume a Nonstop Mediated Decay. LoF is a known mechanism of disease.

BP6

Variant 7-33095235-CA-C is Benign according to our data. Variant chr7-33095235-CA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 198295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1158 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RP9	NM_203288.2 link	c.664delT	p.Ter222AspfsTer29	frameshift_variant, stop_lost	Exon 6 of 6	ENST00000297157.8	NP_976033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RP9	ENST00000297157.8 link	c.664delT	p.Ter222AspfsTer29	frameshift_variant, stop_lost	Exon 6 of 6	1	NM_203288.2	ENSP00000297157.3

Frequencies

GnomAD3 genomes

AF:

0.00762

AC:

1160

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00857

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00623

GnomAD2 exomes

AF:

0.00753

AC:

1857

AN:

246492

AF XY:

0.00753

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.00236

Gnomad ASJ exome

AF:

0.00891

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00705

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00567

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0110

AC:

16044

AN:

1452128

Hom.:

103

Cov.:

AF XY:

0.0108

AC XY:

7844

AN XY:

723066

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

33284

American (AMR)

AF:

0.00309

AC:

138

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00913

AC:

238

AN:

26060

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39628

South Asian (SAS)

AF:

0.00847

AC:

728

AN:

85900

European-Finnish (FIN)

AF:

0.00751

AC:

401

AN:

53408

Middle Eastern (MID)

AF:

0.00487

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0126

AC:

13891

AN:

1103392

Other (OTH)

AF:

0.00939

AC:

564

AN:

60038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

697

1394

2092

2789

3486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.00760

AC:

1158

AN:

152304

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00204

AC:

AN:

41568

American (AMR)

AF:

0.00529

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.00560

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00857

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

820

AN:

68022

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

112

168

224

280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00865

Hom.:

Bravo

AF:

0.00734

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.0105

EpiControl

AF:

0.0103

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RP9: PM4, BS1, BS2

May 18, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

May 05, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinal dystrophy

Benign:1

Jan 01, 2013

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinitis Pigmentosa, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinitis pigmentosa 9

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.3

Mutation Taster

=164/36

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over