rs767210576

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM4BP6_Moderate

The NM_001034853.2(RPGR):c.2946_2951delAGAGGA(p.Glu983_Glu984del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 685,193 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. E982E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 0 hem., cov: 7)

Exomes 𝑓: 0.0000096 ( 0 hom. 2 hem. )

Consequence

RPGR
NM_001034853.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115

Publications

0 publications found

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 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

RPGR links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001034853.2.

BP6

Variant X-38286047-CTCCTCT-C is Benign according to our data. Variant chrX-38286047-CTCCTCT-C is described in ClinVar as Benign. ClinVar VariationId is 237683.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.2946_2951delAGAGGA	p.Glu983_Glu984del	disruptive_inframe_deletion	Exon 15 of 15	ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 link	c.2946_2951delAGAGGA	p.Glu983_Glu984del	disruptive_inframe_deletion	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1 link	c.172-380070_172-380065delTCTTCC		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes

AF:

0.0000347

AC:

AN:

57710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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:

0.0000315

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

50112

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000956

AC:

AN:

627451

Hom.:

AF XY:

0.0000137

AC XY:

AN XY:

146083

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000197

AC:

AN:

15202

American (AMR)

AF:

0.00

AC:

AN:

16707

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10328

East Asian (EAS)

AF:

0.0000487

AC:

AN:

20536

South Asian (SAS)

AF:

0.0000300

AC:

AN:

33327

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18375

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1662

European-Non Finnish (NFE)

AF:

0.00000207

AC:

AN:

483847

Other (OTH)

AF:

0.00

AC:

AN:

27467

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000197943), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.313

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000346

AC:

AN:

57742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

6688

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

13806

American (AMR)

AF:

0.00

AC:

AN:

4951

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1551

East Asian (EAS)

AF:

0.00

AC:

AN:

1453

South Asian (SAS)

AF:

0.00

AC:

AN:

570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2505

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

31711

Other (OTH)

AF:

0.00

AC:

AN:

730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00160

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Oct 22, 2024

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

PhyloP100

0.12

Mutation Taster

=190/10

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over