Variant chr5-64506781-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001029875.3(RGS7BP):c.157T>G(p.Cys53Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RGS7BP
NM_001029875.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

Variant links:

Genes affected

RGS7BP (HGNC:23271): (regulator of G protein signaling 7 binding protein) This gene encodes a protein that binds to all members of the R7 subfamily of regulators of G protein signaling and regulates their translocation between the nucleus and the plasma membrane. The encoded protein could be regulated by reversible palmitoylation, which anchors it to the plasma membrane. Depalmitoylation localizes the protein to the nucleus. Polymorphisms in this gene may be associated with risk of aspirin-exacerbated respiratory disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2012]

RGS7BP links:

RGS7BP (HGNC:):

RGS7BP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS7BP	NM_001029875.3 linkuse as main transcript	c.157T>G	p.Cys53Gly	missense_variant	1/6	ENST00000334025.3	NP_001025046.1	Q6MZT1
RGS7BP	XM_005248502.5 linkuse as main transcript	c.157T>G	p.Cys53Gly	missense_variant	1/5		XP_005248559.1
RGS7BP	XR_948251.4 linkuse as main transcript	n.767T>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS7BP	ENST00000334025.3 linkuse as main transcript	c.157T>G	p.Cys53Gly	missense_variant	1/6	1	NM_001029875.3	ENSP00000334851.2		Q6MZT1
RGS7BP	ENST00000508162.1 linkuse as main transcript	n.525T>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000143

AC:

AN:

1398600

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

690856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000271

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:

9.30e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.157T>G (p.C53G) alteration is located in exon 1 (coding exon 1) of the RGS7BP gene. This alteration results from a T to G substitution at nucleotide position 157, causing the cysteine (C) at amino acid position 53 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Benign

0.87

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.9

REVEL

Uncertain

0.41

Sift

Uncertain

0.017

Sift4G

Uncertain

0.033

Polyphen

0.69

Vest4

0.85

MutPred

0.71

Loss of stability (P = 0.0096);

MVP

0.62

MPC

1.1

ClinPred

0.98

GERP RS

4.0

Varity_R

0.83

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over