7-33095235-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4 BP6_Very_Strong BS2

The NM_203288.2(RP9):c.664del(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:6
• Conservation: PhyloP100: 5.31

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]

LOC124901610 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 224 codons.
• BP6: Variant 7-33095235-CA-C is Benign according to our data. Variant chr7-33095235-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 198295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 1160 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RP9	NM_203288.2	c.664del	p.Ter222AspfsTer29	frameshift_variant, stop_lost	6/6	ENST00000297157.8
LOC124901610	XR_007060277.1	n.1163del		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RP9	ENST00000297157.8	c.664del	p.Ter222AspfsTer29	frameshift_variant, stop_lost	6/6	1	NM_203288.2	P1

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

GnomAD3 exomes AF: 0.00753 AC: 1857 AN: 246492 Hom.: 14 AF XY: 0.00753 AC XY: 1002 AN XY: 133062

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 SAS exome AF: 0.00863

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

Gnomad4 AFR exome AF: 0.00165

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.00913

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00847

Gnomad4 FIN exome AF: 0.00751

Gnomad4 NFE exome AF: 0.0126

Gnomad4 OTH exome AF: 0.00939

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

Gnomad4 AFR AF: 0.00204

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.00616

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 18, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	RP9: PM4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 05, 2015

- -

Retinitis Pigmentosa, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs553265417; hg19: chr7-33134847;