19-32676292-T-A

Position:

chr19-32676292-T-A

Variant summary

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

The NM_207391.3(RGS9BP):c.29T>A(p.Leu10Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,601,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RGS9BP
NM_207391.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS9BP	NM_207391.3 linkuse as main transcript	c.29T>A	p.Leu10Gln	missense_variant	1/1	ENST00000334176.4	NP_997274.2	Q6ZS82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RGS9BP	ENST00000334176.4 linkuse as main transcript	c.29T>A	p.Leu10Gln	missense_variant	1/1	6	NM_207391.3	ENSP00000334134.3	Q6ZS82
ANKRD27	ENST00000590519.2 linkuse as main transcript	c.-537A>T		5_prime_UTR_premature_start_codon_gain_variant	1/4	5		ENSP00000464819.1	K7EIN0
ANKRD27	ENST00000590519.2 linkuse as main transcript	c.-537A>T		5_prime_UTR_variant	1/4	5		ENSP00000464819.1	K7EIN0

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000793

AC:

AN:

239566

Hom.:

AF XY:

0.0000762

AC XY:

AN XY:

131252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

200

AN:

1449068

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

718894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000666

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000179

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 10 of the RGS9BP protein (p.Leu10Gln). This variant is present in population databases (rs773412269, gnomAD 0.02%). 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: 957242). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.39

Sift

Benign

0.13

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.58

MutPred

0.48

Gain of disorder (P = 0.0512);

MVP

0.72

ClinPred

0.51

GERP RS

4.6

Varity_R

0.55

gMVP

0.78

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