2-46576219-C-T

Variant summary

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

The NM_012249.4(RHOQ):​c.334C>T​(p.Pro112Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P112A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RHOQ
NM_012249.4 missense

Scores

7
8
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RHOQNM_012249.4 linkc.334C>T p.Pro112Ser missense_variant Exon 3 of 5 ENST00000238738.9 NP_036381.2 P17081V9HWD0
RHOQXM_011532726.3 linkc.334C>T p.Pro112Ser missense_variant Exon 3 of 6 XP_011531028.1
RHOQXM_005264229.3 linkc.202-4709C>T intron_variant Intron 2 of 2 XP_005264286.1
RHOQ-AS1NR_104182.1 linkn.204+3816G>A intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHOQENST00000238738.9 linkc.334C>T p.Pro112Ser missense_variant Exon 3 of 5 1 NM_012249.4 ENSP00000238738.4 P17081

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1455996
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
724732
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.093
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.73
D;D
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Benign
0.075
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.30
D
MutationAssessor
Uncertain
2.0
M;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-7.3
D;D
REVEL
Uncertain
0.62
Sift
Uncertain
0.014
D;D
Sift4G
Uncertain
0.029
D;D
Polyphen
1.0
D;.
Vest4
0.68
MutPred
0.54
Loss of stability (P = 0.0506);.;
MVP
0.95
MPC
1.8
ClinPred
0.99
D
GERP RS
5.5
Varity_R
0.80
gMVP
0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-46803358; API