rs147388235

Positions:

chrX-38286588-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001034853.2(RPGR):c.2411G>A(p.Arg804Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,041,819 control chromosomes in the GnomAD database, including 26 homozygotes. There are 334 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 9 hom., 37 hem., cov: 8)

Exomes 𝑓: 0.0012 ( 17 hom. 297 hem. )

Consequence

RPGR
NM_001034853.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.17

Variant links:

Genes affected

RPGR (HGNC:10295): (retinitis pigmentosa GTPase regulator) This gene encodes a protein with a series of six RCC1-like domains (RLDs), characteristic of the highly conserved guanine nucleotide exchange factors. The encoded protein is found in the Golgi body and interacts with RPGRIP1. This protein localizes to the outer segment of rod photoreceptors and is essential for their viability. Mutations in this gene have been associated with X-linked retinitis pigmentosa (XLRP). Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported, but the full-length natures of only some have been determined. [provided by RefSeq, Dec 2008]

RPGR 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=0.0029108226).

BP6

Variant X-38286588-C-T is Benign according to our data. Variant chrX-38286588-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 446001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00789 (376/47676) while in subpopulation AFR AF= 0.0305 (353/11571). AF 95% confidence interval is 0.0279. There are 9 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 8. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2 linkuse as main transcript	c.2411G>A	p.Arg804Lys	missense_variant	15/15	ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 linkuse as main transcript	c.2411G>A	p.Arg804Lys	missense_variant	15/15		NM_001034853.2	ENSP00000495537	A2	Q92834-6

Frequencies

GnomAD3 genomes

AF:

0.00789

AC:

376

AN:

47655

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

AN XY:

4485

show subpopulations

Gnomad AFR

AF:

0.0305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00384

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000160

Gnomad OTH

AF:

0.00467

GnomAD3 exomes

AF:

0.00349

AC:

352

AN:

100892

Hom.:

AF XY:

0.00219

AC XY:

AN XY:

30656

show subpopulations

Gnomad AFR exome

AF:

0.0424

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000535

Gnomad OTH exome

AF:

0.00241

GnomAD4 exome

AF:

0.00122

AC:

1212

AN:

994143

Hom.:

Cov.:

AF XY:

0.000965

AC XY:

297

AN XY:

307641

show subpopulations

Gnomad4 AFR exome

AF:

0.0412

Gnomad4 AMR exome

AF:

0.00345

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000398

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00789

AC:

376

AN:

47676

Hom.:

Cov.:

AF XY:

0.00821

AC XY:

AN XY:

4506

show subpopulations

Gnomad4 AFR

AF:

0.0305

Gnomad4 AMR

AF:

0.00383

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000160

Gnomad4 OTH

AF:

0.00458

Alfa

AF:

0.00188

Hom.:

ESP6500AA

AF:

0.0351

AC:

114

ESP6500EA

AF:

0.000539

AC:

ExAC

AF:

0.00407

AC:

136

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Sep 24, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 28, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-1.0

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0030

DANN

Benign

0.44

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.25

.;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

0.23

.;N

REVEL

Benign

0.011

Sift4G

Benign

1.0

.;T

Vest4

0.031

MVP

0.10

MPC

0.79

ClinPred

0.0015

GERP RS

-0.92

gMVP

0.0024

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