ENST00000465127.1:c.172-396489T>A

Variant names:

• chrX-38269632-T-A
• rs779882319
• ENST00000465127.1:c.172-396489T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000465127.1(ENSG00000250349):​c.172-396489T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000095 in 1,158,292 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000057 (0 hom. 2 hem.)
• Consequence: ENSG00000250349 ENST00000465127.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480
• Publications: 0 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, 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-38269632-T-A is Benign according to our data. Variant chrX-38269632-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1802313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465127.1. 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.2442A>T	p.Ile814Ile	synonymous	Exon 19 of 19	NP_000319.1	Q92834-2
	RPGR	NM_001367245.1		c.2439A>T	p.Ile813Ile	synonymous	Exon 19 of 19	NP_001354174.1
	RPGR	NM_001367246.1		c.2256A>T	p.Ile752Ile	synonymous	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.172-396489T>A		intron	N/A	ENSP00000417050.1	B4E171
	RPGR	ENST00000339363.7	TSL:5	c.3057A>T	p.Ile1019Ile	synonymous	Exon 18 of 18	ENSP00000343671.3	Q92834-1
	RPGR	ENST00000642395.2		c.2442A>T	p.Ile814Ile	synonymous	Exon 19 of 19	ENSP00000493468.2	Q92834-2

Frequencies

GnomAD3 genomes AF: 0.0000447 AC: 5 AN: 111831 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000940

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182436 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.00000573 AC: 6 AN: 1046461 Hom.: 0 Cov.: 24 AF XY: 0.00000619 AC XY: 2 AN XY: 323331

African (AFR) AF: 0.00 AC: 0 AN: 25390

American (AMR) AF: 0.00 AC: 0 AN: 35143

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19063

East Asian (EAS) AF: 0.00 AC: 0 AN: 29959

South Asian (SAS) AF: 0.00 AC: 0 AN: 52898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3919

European-Non Finnish (NFE) AF: 0.00000754 AC: 6 AN: 795368

Other (OTH) AF: 0.00 AC: 0 AN: 44427

GnomAD4 genome AF: 0.0000447 AC: 5 AN: 111831 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 34001

African (AFR) AF: 0.00 AC: 0 AN: 30776

American (AMR) AF: 0.00 AC: 0 AN: 10516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3610

South Asian (SAS) AF: 0.00 AC: 0 AN: 2710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5951

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000940 AC: 5 AN: 53197

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.000594 Hom.: 2

Bravo AF: 0.00000756

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.57
PhyloP100		-0.048
Mutation Taster		=100/0	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: rs779882319; hg19: chrX-38128885;