Variant 12-14950705-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001175.7(ARHGDIB):c.8A>G(p.Glu3Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000996 in 1,606,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ARHGDIB
NM_001175.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

Variant links:

Genes affected

ARHGDIB (HGNC:679): (Rho GDP dissociation inhibitor beta) Members of the Rho (or ARH) protein family (see MIM 165390) and other Ras-related small GTP-binding proteins (see MIM 179520) are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The GTP-binding proteins are active only in the GTP-bound state. At least 3 classes of proteins tightly regulate cycling between the GTP-bound and GDP-bound states: GTPase-activating proteins (GAPs), guanine nucleotide-releasing factors (GRFs), and GDP-dissociation inhibitors (GDIs). The GDIs, including ARHGDIB, decrease the rate of GDP dissociation from Ras-like GTPases (summary by Scherle et al., 1993 [PubMed 8356058]).[supplied by OMIM, Dec 2010]

ARHGDIB 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
ARHGDIB	NM_001175.7 linkuse as main transcript	c.8A>G	p.Glu3Gly	missense_variant	2/6	ENST00000228945.9	NP_001166.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGDIB	ENST00000228945.9 linkuse as main transcript	c.8A>G	p.Glu3Gly	missense_variant	2/6	1	NM_001175.7	ENSP00000228945	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

242516

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131184

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:

0.000103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1454318

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

723584

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:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Sep 20, 2023

The c.8A>G (p.E3G) alteration is located in exon 2 (coding exon 1) of the ARHGDIB gene. This alteration results from a A to G substitution at nucleotide position 8, causing the glutamic acid (E) at amino acid position 3 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

Benign

0.11

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;D;D;.;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.57

.;.;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.65

D;D;D;D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.9

M;M;M;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.3

D;D;D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D;D;D;D;D

Sift4G

Benign

0.063

T;T;T;.;.;.

Polyphen

0.82

P;P;P;.;.;.

Vest4

0.55

MutPred

0.51

Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);

MVP

0.71

MPC

0.55

ClinPred

0.94

GERP RS

5.2

Varity_R

0.39

gMVP

0.36

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