rs11279874

Variant names:

• chrX-38269557-CATAAGTT-C
• rs11279874
• ENST00000465127.1:c.172-396559_172-396553delGTTATAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000328.3(RPGR):​c.*62_*68delAACTTAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 814,350 control chromosomes in the GnomAD database, including 257 homozygotes. There are 1,592 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (143 hom., 895 hem., cov: 21)
  • Exomes 𝑓: 0.0042 (114 hom. 697 hem.)
• Consequence: RPGR NM_000328.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.99
• Publications: 1 publications found

Genes affected

ENSG00000250349 (HGNC:):

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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant X-38269557-CATAAGTT-C is Benign according to our data. Variant chrX-38269557-CATAAGTT-C is described in ClinVar as Benign. ClinVar VariationId is 1282240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000328.3. 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_000328.3		c.*62_*68delAACTTAT		3_prime_UTR	Exon 19 of 19	NP_000319.1	Q92834-2
	RPGR	NM_001367245.1		c.*62_*68delAACTTAT		3_prime_UTR	Exon 19 of 19	NP_001354174.1
	RPGR	NM_001367246.1		c.*62_*68delAACTTAT		3_prime_UTR	Exon 18 of 18	NP_001354175.1	Q92834-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-396559_172-396553delGTTATAA		intron	N/A	ENSP00000417050.1	B4E171
	RPGR	ENST00000339363.7	TSL:5	c.*62_*68delAACTTAT		3_prime_UTR	Exon 18 of 18	ENSP00000343671.3	Q92834-1
	RPGR	ENST00000642395.2		c.*62_*68delAACTTAT		3_prime_UTR	Exon 19 of 19	ENSP00000493468.2	Q92834-2

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 3506 AN: 111551 Hom.: 143 Cov.: 21

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00917

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0193

GnomAD4 exome AF: 0.00425 AC: 2984 AN: 702747 Hom.: 114 AF XY: 0.00359 AC XY: 697 AN XY: 194205

African (AFR) AF: 0.121 AC: 2155 AN: 17856

American (AMR) AF: 0.00643 AC: 205 AN: 31882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16572

East Asian (EAS) AF: 0.00969 AC: 262 AN: 27029

South Asian (SAS) AF: 0.000435 AC: 18 AN: 41380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34490

Middle Eastern (MID) AF: 0.00452 AC: 10 AN: 2210

European-Non Finnish (NFE) AF: 0.000164 AC: 82 AN: 498567

Other (OTH) AF: 0.00769 AC: 252 AN: 32761

GnomAD4 genome AF: 0.0314 AC: 3508 AN: 111603 Hom.: 143 Cov.: 21 AF XY: 0.0265 AC XY: 895 AN XY: 33831

African (AFR) AF: 0.107 AC: 3294 AN: 30660

American (AMR) AF: 0.0125 AC: 131 AN: 10516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00920 AC: 33 AN: 3588

South Asian (SAS) AF: 0.00112 AC: 3 AN: 2686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.000338 AC: 18 AN: 53177

Other (OTH) AF: 0.0191 AC: 29 AN: 1519

Alfa AF: 0.0244 Hom.: 77

Bravo AF: 0.0380

Asia WGS AF: 0.00880 AC: 22 AN: 2510

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11279874; hg19: chrX-38128810;