11-3827718-G-T

Variant summary

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

The NM_001665.4(RHOG):​c.421C>A​(p.Gln141Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RHOG
NM_001665.4 missense

Scores

13
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RHOGNM_001665.4 linkc.421C>A p.Gln141Lys missense_variant 2/2 ENST00000351018.5 NP_001656.2 P84095Q6ICQ8
RHOGXM_005252916.3 linkc.421C>A p.Gln141Lys missense_variant 2/2 XP_005252973.1 P84095Q6ICQ8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RHOGENST00000351018.5 linkc.421C>A p.Gln141Lys missense_variant 2/21 NM_001665.4 ENSP00000339467.4 P84095
RHOGENST00000396978.1 linkc.421C>A p.Gln141Lys missense_variant 2/23 ENSP00000380175.1 P84095
RHOGENST00000396979.1 linkc.421C>A p.Gln141Lys missense_variant 2/23 ENSP00000380176.1 P84095
RHOGENST00000533217.1 linkc.421C>A p.Gln141Lys missense_variant 2/25 ENSP00000436932.1 P84095

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152256
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250352
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135470
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461690
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152256
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsDec 20, 2023The c.421C>A (p.Q141K) alteration is located in exon 2 (coding exon 1) of the RHOG gene. This alteration results from a C to A substitution at nucleotide position 421, causing the glutamine (Q) at amino acid position 141 to be replaced by a lysine (K). 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
Uncertain
0.53
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.52
D;D;D;D
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
.;.;.;D
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Benign
1.6
L;L;L;L
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.5
D;D;D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.018
D;D;D;D
Sift4G
Benign
0.064
T;T;T;T
Polyphen
0.16
B;B;B;B
Vest4
0.54
MVP
0.80
MPC
2.7
ClinPred
0.86
D
GERP RS
5.5
Varity_R
0.89
gMVP
0.88

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.

Other links and lift over

dbSNP: rs370498764; hg19: chr11-3848948; API