rs62636730

Variant names:

Variant summary

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

The NM_001034853.2(RPGR):c.3231T>A(p.Asn1077Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,207,070 control chromosomes in the GnomAD database, including 288 homozygotes. There are 9,240 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 0.020 ( 38 hom., 597 hem., cov: 21)

Exomes 𝑓: 0.025 ( 250 hom. 8643 hem. )

Consequence

RPGR
NM_001034853.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.807

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=0.0013820231).

BP6

Variant X-38285768-A-T is Benign according to our data. Variant chrX-38285768-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 403392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38285768-A-T is described in Lovd as [Likely_benign]. Variant chrX-38285768-A-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0202 (2201/109016) while in subpopulation NFE AF= 0.0291 (1525/52342). AF 95% confidence interval is 0.0279. There are 38 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.3231T>A	p.Asn1077Lys	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.3231T>A	p.Asn1077Lys	missense_variant	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 link	c.172-380353A>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

2201

AN:

108960

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

596

AN XY:

31532

show subpopulations

Gnomad AFR

AF:

0.00369

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.0165

Gnomad ASJ

AF:

0.0424

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00162

Gnomad FIN

AF:

0.0194

Gnomad MID

AF:

0.0386

Gnomad NFE

AF:

0.0291

Gnomad OTH

AF:

0.0156

GnomAD3 exomes

AF:

0.0193

AC:

3507

AN:

182026

Hom.:

AF XY:

0.0194

AC XY:

1304

AN XY:

67264

show subpopulations

Gnomad AFR exome

AF:

0.00403

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0443

Gnomad EAS exome

AF:

0.000144

Gnomad SAS exome

AF:

0.00320

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0245

AC:

26913

AN:

1098054

Hom.:

250

Cov.:

AF XY:

0.0238

AC XY:

8643

AN XY:

363452

show subpopulations

Gnomad4 AFR exome

AF:

0.00394

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.0418

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00345

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0276

Gnomad4 OTH exome

AF:

0.0232

GnomAD4 genome

AF:

0.0202

AC:

2201

AN:

109016

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

597

AN XY:

31598

show subpopulations

Gnomad4 AFR

AF:

0.00368

Gnomad4 AMR

AF:

0.0165

Gnomad4 ASJ

AF:

0.0424

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00163

Gnomad4 FIN

AF:

0.0194

Gnomad4 NFE

AF:

0.0291

Gnomad4 OTH

AF:

0.0155

Alfa

AF:

0.0278

Hom.:

223

Bravo

AF:

0.0190

TwinsUK

AF:

0.0264

AC:

ALSPAC

AF:

0.0322

AC:

ESP6500AA

AF:

0.00287

AC:

ESP6500EA

AF:

0.0293

AC:

197

ExAC

AF:

0.0196

AC:

2384

EpiCase

AF:

0.0282

EpiControl

AF:

0.0289

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 06, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely 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 -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.99

BayesDel_noAF

Benign

-1.2

CADD

Benign

DANN

Benign

0.94

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.28

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.81

.;N

REVEL

Benign

0.050

Sift4G

Benign

0.67

.;T

Vest4

0.031

MutPred

0.39

Gain of methylation at N1077 (P = 0.005);Gain of methylation at N1077 (P = 0.005);

MPC

0.90

ClinPred

0.0062

GERP RS

1.6

gMVP

0.015

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