2-46576594-A-G

Variant summary

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

The NM_012249.4(RHOQ):​c.400A>G​(p.Arg134Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RHOQ
NM_012249.4 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13
Variant links:
Genes affected
RHOQ (HGNC:17736): (ras homolog family member Q) 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 is an important signalling protein for sarcomere assembly and has been shown to play a significant role in the exocytosis of the solute carrier family 2, facilitated glucose transporter member 4 and other proteins, possibly acting as the signal that turns on the membrane fusion machinery. Three related pseudogene have been identified on chromosomes 2 and 14. [provided by RefSeq, Aug 2011]
RHOQ-AS1 (HGNC:40816): (RHOQ antisense RNA 1)

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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
RHOQNM_012249.4 linkuse as main transcriptc.400A>G p.Arg134Gly missense_variant 4/5 ENST00000238738.9 NP_036381.2
RHOQ-AS1NR_104182.1 linkuse as main transcriptn.204+3441T>C intron_variant, non_coding_transcript_variant
RHOQXM_011532726.3 linkuse as main transcriptc.400A>G p.Arg134Gly missense_variant 4/6 XP_011531028.1
RHOQXM_005264229.3 linkuse as main transcriptc.202-4334A>G intron_variant XP_005264286.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RHOQENST00000238738.9 linkuse as main transcriptc.400A>G p.Arg134Gly missense_variant 4/51 NM_012249.4 ENSP00000238738 P1
RHOQ-AS1ENST00000506009.2 linkuse as main transcriptn.204+3441T>C intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

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 GeneticsMay 09, 2023The c.400A>G (p.R134G) alteration is located in exon 4 (coding exon 4) of the RHOQ gene. This alteration results from a A to G substitution at nucleotide position 400, causing the arginine (R) at amino acid position 134 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
Uncertain
0.52
BayesDel_addAF
Uncertain
0.030
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D;D
Eigen
Benign
0.11
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.049
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.033
D;D
Polyphen
0.14
B;.
Vest4
0.46
MutPred
0.57
Loss of stability (P = 0.0238);.;
MVP
0.82
MPC
1.3
ClinPred
0.98
D
GERP RS
4.4
Varity_R
0.65
gMVP
0.55

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.

Other links and lift over

hg19: chr2-46803733; API