X-38285569-C-T

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.3430G>A(p.Val1144Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,209,237 control chromosomes in the GnomAD database, including 6,166 homozygotes. There are 41,850 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 530 hom., 3031 hem., cov: 22)

Exomes 𝑓: 0.10 ( 5636 hom. 38819 hem. )

Consequence

RPGR
NM_001034853.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.95

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=0.0035799146).

BP6

Variant X-38285569-C-T is Benign according to our data. Variant chrX-38285569-C-T is described in ClinVar as [Benign]. Clinvar id is 403388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38285569-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.3430G>A	p.Val1144Ile	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.3430G>A	p.Val1144Ile	missense_variant	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 link	c.172-380552C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

9602

AN:

111316

Hom.:

529

Cov.:

AF XY:

0.0903

AC XY:

3029

AN XY:

33526

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.0808

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0762

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.0949

Gnomad MID

AF:

0.0210

Gnomad NFE

AF:

0.0833

Gnomad OTH

AF:

0.0747

GnomAD3 exomes

AF:

0.140

AC:

25623

AN:

183049

Hom.:

1863

AF XY:

0.139

AC XY:

9410

AN XY:

67631

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.0814

Gnomad EAS exome

AF:

0.404

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.0958

Gnomad NFE exome

AF:

0.0828

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.103

AC:

113119

AN:

1097871

Hom.:

5636

Cov.:

AF XY:

0.107

AC XY:

38819

AN XY:

363459

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.0805

Gnomad4 EAS exome

AF:

0.412

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.0971

Gnomad4 NFE exome

AF:

0.0830

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0862

AC:

9605

AN:

111366

Hom.:

530

Cov.:

AF XY:

0.0902

AC XY:

3031

AN XY:

33586

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.0762

Gnomad4 EAS

AF:

0.391

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.0949

Gnomad4 NFE

AF:

0.0833

Gnomad4 OTH

AF:

0.0804

Alfa

AF:

0.0921

Hom.:

6105

Bravo

AF:

0.0903

TwinsUK

AF:

0.0817

AC:

303

ALSPAC

AF:

0.0865

AC:

250

ESP6500AA

AF:

0.0183

AC:

ESP6500EA

AF:

0.0865

AC:

582

ExAC

AF:

0.138

AC:

16713

EpiCase

AF:

0.0712

EpiControl

AF:

0.0730

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 27, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

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: MAF -

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

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.92

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.29

.;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.27

.;N

REVEL

Benign

0.081

Sift4G

Pathogenic

0.0

.;D

Vest4

0.10

MPC

0.63

ClinPred

0.018

GERP RS

2.7

gMVP

0.085

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