rs34117835

chrX-38269772-G-AchrX-38269772-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000339363.7(RPGR):c.2917C>T(p.Pro973Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P973L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: RPGR ENST00000339363.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18268338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_000328.3	c.2302C>T	p.Pro768Ser	missense_variant	19/19
RPGR	NM_001367245.1	c.2299C>T	p.Pro767Ser	missense_variant	19/19
RPGR	NM_001367246.1	c.2116C>T	p.Pro706Ser	missense_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000339363.7	c.2917C>T	p.Pro973Ser	missense_variant	18/18	5		P4
RPGR	ENST00000642395.2	c.2302C>T	p.Pro768Ser	missense_variant	19/19			A2
RPGR	ENST00000644337.1	c.2116C>T	p.Pro706Ser	missense_variant	18/18

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	19
Dann	Benign	0.93
FATHMM_MKL	Benign	0.70	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Uncertain	-2.6	D;.;N;.;.
REVEL	Benign	0.068
Sift	Benign	0.051	T;.;D;.;.
Sift4G	Benign	0.078	T;.;T;.;.
Polyphen		0.85	P;P;.;.;.
Vest4		0.21
MutPred		0.25		Loss of helix (P = 0.028);Loss of helix (P = 0.028);.;.;.;
MVP		0.17
ClinPred		0.41	T
GERP RS		3.3
Varity_R		0.065

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: rs34117835; hg19: chrX-38129025; COSMIC: COSV58839334; COSMIC: COSV58839334;