Variant 11-3827993-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001665.4(RHOG):c.146G>A(p.Arg49His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RHOG
NM_001665.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

RHOG (HGNC:672): (ras homolog family member G) This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The encoded protein facilitates translocation of a functional guanine nucleotide exchange factor (GEF) complex from the cytoplasm to the plasma membrane where ras-related C3 botulinum toxin substrate 1 is activated to promote lamellipodium formation and cell migration. Two related pseudogene have been identified on chromosomes 20 and X. [provided by RefSeq, Aug 2011]

RHOG links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOG	NM_001665.4 linkuse as main transcript	c.146G>A	p.Arg49His	missense_variant	2/2	ENST00000351018.5	NP_001656.2	P84095Q6ICQ8
RHOG	XM_005252916.3 linkuse as main transcript	c.146G>A	p.Arg49His	missense_variant	2/2		XP_005252973.1	P84095Q6ICQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHOG	ENST00000351018.5 linkuse as main transcript	c.146G>A	p.Arg49His	missense_variant	2/2	1	NM_001665.4	ENSP00000339467.4	P84095
RHOG	ENST00000396978.1 linkuse as main transcript	c.146G>A	p.Arg49His	missense_variant	2/2	3		ENSP00000380175.1	P84095
RHOG	ENST00000396979.1 linkuse as main transcript	c.146G>A	p.Arg49His	missense_variant	2/2	3		ENSP00000380176.1	P84095
RHOG	ENST00000533217.1 linkuse as main transcript	c.146G>A	p.Arg49His	missense_variant	2/2	5		ENSP00000436932.1	P84095

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251470

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

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:

1461892

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Aug 16, 2021

The c.146G>A (p.R49H) alteration is located in exon 2 (coding exon 1) of the RHOG gene. This alteration results from a G to A substitution at nucleotide position 146, causing the arginine (R) at amino acid position 49 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;D;D;D

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

.;.;.;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.60

D;D;D;D

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.4

L;L;L;L

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Uncertain

0.50

Sift

Benign

0.056

T;T;T;T

Sift4G

Benign

0.076

T;T;T;T

Polyphen

0.022

B;B;B;B

Vest4

0.67

MutPred

0.40

Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);

MVP

0.89

MPC

1.5

ClinPred

0.72

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.72

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