chr19-32676628-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207391.3(RGS9BP):c.365C>G(p.Ser122Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,530,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S122S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

RGS9BP
NM_207391.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

RGS9BP (HGNC:30304): (regulator of G protein signaling 9 binding protein) The protein encoded by this gene functions as a regulator of G protein-coupled receptor signaling in phototransduction. Studies in bovine and mouse show that this gene is expressed only in the retina, and is localized in the rod outer segment membranes. This protein is associated with a heterotetrameric complex, specifically interacting with the regulator of G-protein signaling 9, and appears to function as the membrane anchor for the other largely soluble interacting partners. Mutations in this gene are associated with prolonged electroretinal response suppression (PERRS), also known as bradyopsia. [provided by RefSeq, Mar 2010]

RGS9BP links:

ANKRD27 (HGNC:25310): (ankyrin repeat domain 27) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endocytic recycling and negative regulation of SNARE complex assembly. Acts upstream of or within early endosome to late endosome transport. Located in endosome; lysosome; and plasma membrane. Implicated in eosinophilic esophagitis. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.20918679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS9BP	NM_207391.3 link	c.365C>G	p.Ser122Cys	missense_variant	Exon 1 of 1	ENST00000334176.4	NP_997274.2	Q6ZS82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS9BP	ENST00000334176.4 link	c.365C>G	p.Ser122Cys	missense_variant	Exon 1 of 1	6	NM_207391.3	ENSP00000334134.3		Q6ZS82
ANKRD27	ENST00000590519.2 link	c.-873G>C		upstream_gene_variant		5		ENSP00000464819.1		K7EIN0

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000795

AC:

AN:

125808

Hom.:

AF XY:

0.000116

AC XY:

AN XY:

68872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000454

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1378492

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

679748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000419

Gnomad4 FIN exome

AF:

0.0000299

Gnomad4 NFE exome

AF:

0.00000929

Gnomad4 OTH exome

AF:

0.0000695

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 122 of the RGS9BP protein (p.Ser122Cys). This variant is present in population databases (rs749927570, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with RGS9BP-related conditions. ClinVar contains an entry for this variant (Variation ID: 522947). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Bradyopsia

Uncertain:2

Jan 05, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 03, 2020

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Uncertain:1

Jan 01, 2022

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.41

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.71

M_CAP

Benign

0.069

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.13

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.014

Polyphen

0.85

Vest4

0.11

MutPred

0.42

Loss of glycosylation at S122 (P = 0.003);

MVP

0.76

ClinPred

0.69

GERP RS

2.5

Varity_R

0.20

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over