rs866718135

Positions:

• chrX-38299117-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001034853.2(RPGR):​c.1084G>A​(p.Val362Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RPGR NM_001034853.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1661993).
• BP6: Variant X-38299117-C-T is Benign according to our data. Variant chrX-38299117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255829.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2	c.1084G>A	p.Val362Ile	missense_variant	10/15	ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1	c.1084G>A	p.Val362Ile	missense_variant	10/15		NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	c.172-367004C>T		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.3
DANN	Benign	0.92
DEOGEN2	Benign	0.13	.;.;T;.;.;.
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	.;T;T;.;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L;L;L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.42	N;.;N;.;N;.
REVEL	Benign	0.16
Sift	Benign	0.12	T;.;T;.;.;.
Sift4G	Benign	0.28	T;.;T;.;D;.
Polyphen		0.097	B;B;.;.;.;.
Vest4		0.21
MutPred		0.30		Loss of catalytic residue at V362 (P = 0.0055);Loss of catalytic residue at V362 (P = 0.0055);Loss of catalytic residue at V362 (P = 0.0055);Loss of catalytic residue at V362 (P = 0.0055);Loss of catalytic residue at V362 (P = 0.0055);.;
MVP		0.28
MPC		0.78
ClinPred		0.18	T
GERP RS		-1.1
Varity_R		0.087
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs866718135; hg19: chrX-38158370;