7-33095271-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_203288.2(RP9):c.629A>G(p.Lys210Arg) variant causes a missense change. The variant allele was found at a frequency of 0.219 in 1,611,264 control chromosomes in the GnomAD database, including 40,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2559 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37737 hom. )

Consequence

RP9
NM_203288.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.86

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 links:

LOC124901610 (HGNC:):

LOC124901610 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014506578).

BP6

Variant 7-33095271-T-C is Benign according to our data. Variant chr7-33095271-T-C is described in ClinVar as [Benign]. Clinvar id is 167609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RP9	NM_203288.2 linkuse as main transcript	c.629A>G	p.Lys210Arg	missense_variant	6/6	ENST00000297157.8
LOC124901610	XR_007060277.1 linkuse as main transcript	n.1198T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RP9	ENST00000297157.8 linkuse as main transcript	c.629A>G	p.Lys210Arg	missense_variant	6/6	1	NM_203288.2	P1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25764

AN:

151870

Hom.:

2562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.204

AC:

50521

AN:

247162

Hom.:

5707

AF XY:

0.217

AC XY:

28922

AN XY:

133576

show subpopulations

Gnomad AFR exome

AF:

0.0538

Gnomad AMR exome

AF:

0.0992

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.266

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.224

AC:

327481

AN:

1459276

Hom.:

37737

Cov.:

AF XY:

0.228

AC XY:

165618

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.0521

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.214

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.169

AC:

25761

AN:

151988

Hom.:

2559

Cov.:

AF XY:

0.170

AC XY:

12657

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0576

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.221

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.197

Hom.:

552

Bravo

AF:

0.158

ESP6500AA

AF:

0.0629

AC:

277

ESP6500EA

AF:

0.222

AC:

1898

ExAC

AF:

0.207

AC:

25076

EpiCase

AF:

0.221

EpiControl

AF:

0.218

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis pigmentosa 9

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 07, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

Cadd

Uncertain

Dann

Benign

0.95

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.071

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.1

REVEL

Benign

0.26

Sift

Benign

0.22

Sift4G

Uncertain

0.043

Polyphen

0.97

Vest4

0.11

MPC

0.74

ClinPred

0.037

GERP RS

3.8

Varity_R

0.087

gMVP

0.0051

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