rs150549982

Variant names:

• chrX-38298961-C-G
• rs150549982
• NM_001034853.2:c.1240G>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

This summary comes from the ClinGen Evidence Repository: NM_001034853.2(RPGR):c.1240G>C is a missense variant predicted to cause the substitution of glutamate by glutamine at amino acid 414. This variant is present in gnomAD v.4.1.0 at a frequency of 0.00008303 among hemizygous individuals, with 33 variant alleles / 397,426 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1). The computational predictor REVEL gives a score of 0.119, which is below the ClinGen X-linked IRD VCEP threshold of < 0.183 and predicts a non-damaging effect on the RPGR function. Additionally, the splicing impact predictor SpliceAI gives a delta score of 0.02, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4_moderate). In summary, this variant is classified as benign for RPGR-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen X-linked IRD VCEP: BA1, and BP4_moderate. (VCEP specifications version 1.0.0; date of approval 05/16/2025). LINK:https://erepo.genome.network/evrepo/ui/classification/CA10385514/MONDO:0100437/106

• Frequency:
  • Genomes: 𝑓 0.00047 (1 hom., 11 hem., cov: 23)
  • Exomes 𝑓: 0.000059 (0 hom. 22 hem.)
• Consequence: RPGR NM_001034853.2 missense
• Clinical Significance: Benign reviewed by expert panel B:5
• Conservation: PhyloP100: 4.09
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 3

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• RPGR-related retinopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• primary ciliary dyskinesia-retinitis pigmentosa syndrome

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• macular degeneration, X-linked atrophic

  Inheritance: XL Classification: LIMITED Submitted by: G2P

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034853.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGR	NM_001034853.2	MANE Select	c.1240G>C	p.Glu414Gln	missense	Exon 10 of 15	NP_001030025.1	Q92834-6
	RPGR	NM_000328.3		c.1240G>C	p.Glu414Gln	missense	Exon 10 of 19	NP_000319.1	Q92834-2
	RPGR	NM_001367245.1		c.1237G>C	p.Glu413Gln	missense	Exon 10 of 19	NP_001354174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGR	ENST00000645032.1	MANE Select	c.1240G>C	p.Glu414Gln	missense	Exon 10 of 15	ENSP00000495537.1	Q92834-6
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-367160C>G		intron	N/A	ENSP00000417050.1	B4E171
	RPGR	ENST00000494841.1	TSL:1	n.503G>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 53 AN: 111966 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000158 AC: 29 AN: 183397 AF XY: 0.000118

Gnomad AFR exome AF: 0.00182

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000592 AC: 65 AN: 1097871 Hom.: 0 Cov.: 30 AF XY: 0.0000606 AC XY: 22 AN XY: 363247

African (AFR) AF: 0.00182 AC: 48 AN: 26402

American (AMR) AF: 0.000170 AC: 6 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841804

Other (OTH) AF: 0.000195 AC: 9 AN: 46083

GnomAD4 genome AF: 0.000473 AC: 53 AN: 112019 Hom.: 1 Cov.: 23 AF XY: 0.000322 AC XY: 11 AN XY: 34179

African (AFR) AF: 0.00169 AC: 52 AN: 30845

American (AMR) AF: 0.00 AC: 0 AN: 10529

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3598

South Asian (SAS) AF: 0.00 AC: 0 AN: 2698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53238

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.000285 Hom.: 1

Bravo AF: 0.000536

ESP6500AA AF: 0.000783 AC: 3

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.000198 AC: 24

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	RPGR-related retinopathy (1)
-	-	1	X-linked cone-rod dystrophy 1;C1845667:Retinitis pigmentosa 3;C2749137:Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness;C3151784:Macular degeneration, X-linked atrophic (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.1
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.12
Sift	Benign	0.082	T
Sift4G	Benign	0.073	T
Polyphen		1.0	D
Vest4		0.48
MVP		0.42
MPC		0.17
ClinPred		0.042	T
GERP RS		5.3
Varity_R		0.47
gMVP		0.50
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs150549982; hg19: chrX-38158214;