rs201730068

Variant names:

• chrX-38286662-TTCC-T
• rs201730068
• NM_001034853.2:c.2334_2336delGGA

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The NM_001034853.2(RPGR):​c.2334_2336delGGA​(p.Glu779del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,123,100 control chromosomes in the GnomAD database, including 35 homozygotes. There are 446 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (16 hom., 82 hem., cov: 12)
  • Exomes 𝑓: 0.0013 (19 hom. 364 hem.)
• Consequence: RPGR NM_001034853.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.518
• Publications: 0 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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001034853.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant X-38286662-TTCC-T is Benign according to our data. Variant chrX-38286662-TTCC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.01 (777/77436) while in subpopulation AFR AF = 0.0353 (696/19714). AF 95% confidence interval is 0.0331. There are 16 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position passed quality control check.
• BS2: High AC in GnomAd4 at 777 XL,AD gene.

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.2334_2336delGGA	p.Glu779del	disruptive_inframe_deletion	Exon 15 of 15	NP_001030025.1	Q92834-6
	RPGR	NM_000328.3		c.1905+429_1905+431delGGA		intron	N/A	NP_000319.1	Q92834-2
	RPGR	NM_001367245.1		c.1902+429_1902+431delGGA		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.2334_2336delGGA	p.Glu779del	disruptive_inframe_deletion	Exon 15 of 15	ENSP00000495537.1	Q92834-6
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-379454_172-379452delCCT		intron	N/A	ENSP00000417050.1	B4E171
	RPGR	ENST00000339363.7	TSL:5	c.2520+429_2520+431delGGA		intron	N/A	ENSP00000343671.3	Q92834-1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 777 AN: 77394 Hom.: 16 Cov.: 12

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00948

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: 0.000124

Gnomad OTH AF: 0.0117

GnomAD2 exomes AF: 0.00398 AC: 451 AN: 113351 AF XY: 0.00271

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.00512

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000850

Gnomad NFE exome AF: 0.0000470

Gnomad OTH exome AF: 0.00275

GnomAD4 exome AF: 0.00132 AC: 1379 AN: 1045664 Hom.: 19 AF XY: 0.00107 AC XY: 364 AN XY: 339624

African (AFR) AF: 0.0406 AC: 1000 AN: 24635

American (AMR) AF: 0.00575 AC: 159 AN: 27673

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18409

East Asian (EAS) AF: 0.00 AC: 0 AN: 26652

South Asian (SAS) AF: 0.000242 AC: 12 AN: 49652

European-Finnish (FIN) AF: 0.0000537 AC: 2 AN: 37269

Middle Eastern (MID) AF: 0.000342 AC: 1 AN: 2924

European-Non Finnish (NFE) AF: 0.0000601 AC: 49 AN: 814632

Other (OTH) AF: 0.00356 AC: 156 AN: 43818

GnomAD4 genome AF: 0.0100 AC: 777 AN: 77436 Hom.: 16 Cov.: 12 AF XY: 0.00688 AC XY: 82 AN XY: 11918

African (AFR) AF: 0.0353 AC: 696 AN: 19714

American (AMR) AF: 0.00946 AC: 64 AN: 6765

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2034

East Asian (EAS) AF: 0.00 AC: 0 AN: 2270

South Asian (SAS) AF: 0.00 AC: 0 AN: 1118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 127

European-Non Finnish (NFE) AF: 0.000124 AC: 5 AN: 40414

Other (OTH) AF: 0.0115 AC: 12 AN: 1043

Alfa AF: 0.00652 Hom.: 32

Asia WGS AF: 0.00159 AC: 4 AN: 2521

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.52
Mutation Taster		=90/10	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: rs201730068; hg19: chrX-38145915;