chr7-33095235-CA-C

Variant names:

• chr7-33095235-CA-C
• rs553265417
• NM_203288.2:c.664delT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 8P and 12B. PVS1 BP6_Very_Strong BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 5.31
• Publications: 5 publications found

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

ENSG00000302625 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203288.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP9	NM_203288.2	MANE Select	c.664delT	p.Ter222AspfsTer29	frameshift stop_lost	Exon 6 of 6	NP_976033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP9	ENST00000297157.8	TSL:1 MANE Select	c.664delT	p.Ter222AspfsTer29	frameshift stop_lost	Exon 6 of 6	ENSP00000297157.3
	RP9	ENST00000474370.2	TSL:2	n.2637delT		non_coding_transcript_exon	Exon 5 of 5
	RP9	ENST00000492391.2	TSL:3	n.1788delT		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00762 AC: 1160 AN: 152186 Hom.: 10 Cov.: 32

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

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.: 28 AF XY: 0.0108 AC XY: 7844 AN XY: 723066

African (AFR) AF: 0.00165 AC: 55 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: 1 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: 28 AN: 5744

European-Non Finnish (NFE) AF: 0.0126 AC: 13891 AN: 1103392

Other (OTH) AF: 0.00939 AC: 564 AN: 60038

GnomAD4 genome AF: 0.00760 AC: 1158 AN: 152304 Hom.: 10 Cov.: 32 AF XY: 0.00720 AC XY: 536 AN XY: 74466

African (AFR) AF: 0.00204 AC: 85 AN: 41568

American (AMR) AF: 0.00529 AC: 81 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4824

European-Finnish (FIN) AF: 0.00857 AC: 91 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0121 AC: 820 AN: 68022

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00865 Hom.: 2

Bravo AF: 0.00734

Asia WGS AF: 0.00173 AC: 6 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

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3
Mutation Taster		=164/36	polymorphism

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: rs553265417; hg19: chr7-33134847;