NM_001034853.2:c.2341G>A

Variant names:

Variant summary

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

The NM_001034853.2(RPGR):c.2341G>A(p.Ala781Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,131,478 control chromosomes in the GnomAD database, including 10,907 homozygotes. There are 54,741 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 Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 785 hom., 1169 hem., cov: 11)

Exomes 𝑓: 0.16 ( 10122 hom. 53572 hem. )

Consequence

RPGR
NM_001034853.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.308

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:

ENSG00000250349 (HGNC:):

ENSG00000250349 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=0.00457561).

BP6

Variant X-38286658-C-T is Benign according to our data. Variant chrX-38286658-C-T is described in ClinVar as [Benign]. Clinvar id is 257193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38286658-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.2341G>A	p.Ala781Thr	missense_variant	Exon 15 of 15	ENST00000645032.1	NP_001030025.1	Q92834-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 link	c.2341G>A	p.Ala781Thr	missense_variant	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 link	c.172-379463C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

10242

AN:

79301

Hom.:

784

Cov.:

AF XY:

0.0989

AC XY:

1170

AN XY:

11831

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.0992

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.122

AC:

13768

AN:

113184

Hom.:

748

AF XY:

0.119

AC XY:

4758

AN XY:

40122

show subpopulations

Gnomad AFR exome

AF:

0.0862

Gnomad AMR exome

AF:

0.0876

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0418

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.160

AC:

168047

AN:

1052147

Hom.:

10122

Cov.:

AF XY:

0.156

AC XY:

53572

AN XY:

344163

show subpopulations

Gnomad4 AFR exome

AF:

0.0877

Gnomad4 AMR exome

AF:

0.0916

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.000258

Gnomad4 SAS exome

AF:

0.0439

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.129

AC:

10238

AN:

79331

Hom.:

785

Cov.:

AF XY:

0.0986

AC XY:

1169

AN XY:

11861

show subpopulations

Gnomad4 AFR

AF:

0.0815

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.0992

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.168

Hom.:

9629

Bravo

AF:

0.135

TwinsUK

AF:

0.174

AC:

646

ALSPAC

AF:

0.173

AC:

501

ESP6500AA

AF:

0.0842

AC:

280

ESP6500EA

AF:

0.169

AC:

973

ExAC

AF:

0.0834

AC:

3127

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 29, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

May 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-1.1

BayesDel_noAF

Benign

-1.2

CADD

Benign

4.7

DANN

Benign

0.80

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.23

.;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.20

PROVEAN

Benign

0.10

.;N

REVEL

Benign

0.059

Sift4G

Benign

0.61

.;T

Vest4

0.028

MPC

0.76

ClinPred

0.00093

GERP RS

-2.2

gMVP

0.0030

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