rs6651585

Variant names:

• chrX-38323539-C-T
• rs6651585
• NM_001034853.2:c.29-15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001034853.2(RPGR):​c.29-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,202,845 control chromosomes in the GnomAD database, including 14,961 homozygotes. There are 59,659 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (2750 hom., 7210 hem., cov: 22)
  • Exomes 𝑓: 0.14 (12211 hom. 52449 hem.)
• Consequence: RPGR NM_001034853.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.50
• Publications: 6 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)
• RPGR-related retinopathy

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

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-38323539-C-T is Benign according to our data. Variant chrX-38323539-C-T is described in ClinVar as Benign. ClinVar VariationId is 92856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

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.29-15G>A		intron	N/A	NP_001030025.1
	RPGR	NM_000328.3		c.29-15G>A		intron	N/A	NP_000319.1
	RPGR	NM_001367245.1		c.29-15G>A		intron	N/A	NP_001354174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGR	ENST00000645032.1	MANE Select	c.29-15G>A		intron	N/A	ENSP00000495537.1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-342582C>T		intron	N/A	ENSP00000417050.1
	RPGR	ENST00000339363.7	TSL:5	c.29-15G>A		intron	N/A	ENSP00000343671.3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 24233 AN: 110988 Hom.: 2741 Cov.: 22

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.0751

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.218 AC: 39354 AN: 180770 AF XY: 0.201

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.625

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.144 AC: 156798 AN: 1091805 Hom.: 12211 Cov.: 29 AF XY: 0.146 AC XY: 52449 AN XY: 359101

African (AFR) AF: 0.392 AC: 10256 AN: 26192

American (AMR) AF: 0.314 AC: 10995 AN: 35065

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2311 AN: 19317

East Asian (EAS) AF: 0.640 AC: 19219 AN: 30047

South Asian (SAS) AF: 0.294 AC: 15835 AN: 53817

European-Finnish (FIN) AF: 0.107 AC: 4337 AN: 40411

Middle Eastern (MID) AF: 0.0908 AC: 272 AN: 2996

European-Non Finnish (NFE) AF: 0.102 AC: 85644 AN: 838198

Other (OTH) AF: 0.173 AC: 7929 AN: 45762

GnomAD4 genome AF: 0.219 AC: 24275 AN: 111040 Hom.: 2750 Cov.: 22 AF XY: 0.216 AC XY: 7210 AN XY: 33316

African (AFR) AF: 0.388 AC: 11810 AN: 30435

American (AMR) AF: 0.258 AC: 2713 AN: 10498

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 297 AN: 2641

East Asian (EAS) AF: 0.619 AC: 2153 AN: 3476

South Asian (SAS) AF: 0.319 AC: 848 AN: 2656

European-Finnish (FIN) AF: 0.105 AC: 618 AN: 5913

Middle Eastern (MID) AF: 0.0968 AC: 21 AN: 217

European-Non Finnish (NFE) AF: 0.103 AC: 5470 AN: 53010

Other (OTH) AF: 0.194 AC: 294 AN: 1515

Alfa AF: 0.142 Hom.: 4524

Bravo AF: 0.243

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.78
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs6651585; hg19: chrX-38182792; COSMIC: COSV58840169; COSMIC: COSV58840169;