chr2-46543059-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012249.4(RHOQ):c.13C>T(p.Pro5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RHOQ
NM_012249.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.146

Publications

0 publications found

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13668528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOQ	NM_012249.4 link	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 5	ENST00000238738.9	NP_036381.2	P17081V9HWD0
RHOQ	XM_011532726.3 link	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 6		XP_011531028.1
RHOQ	XM_005264229.3 link	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 3		XP_005264286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHOQ	ENST00000238738.9 link	c.13C>T	p.Pro5Ser	missense_variant	Exon 1 of 5	1	NM_012249.4	ENSP00000238738.4	P17081
RHOQ	ENST00000432183.5 link	n.13C>T		non_coding_transcript_exon_variant	Exon 1 of 3	5		ENSP00000393140.1	F8WET9
RHOQ	ENST00000465198.1 link	n.155+1099C>T		intron_variant	Intron 1 of 1	3
RHOQ	ENST00000489471.5 link	n.-90C>T		upstream_gene_variant		5		ENSP00000428624.1	H0YB40

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000138

AC:

AN:

1449842

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32060

American (AMR)

AF:

0.00

AC:

AN:

44110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25674

East Asian (EAS)

AF:

0.00

AC:

AN:

38218

South Asian (SAS)

AF:

0.00

AC:

AN:

85162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4856

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107744

Other (OTH)

AF:

0.00

AC:

AN:

59860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 14, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.13C>T (p.P5S) alteration is located in exon 1 (coding exon 1) of the RHOQ gene. This alteration results from a C to T substitution at nucleotide position 13, causing the proline (P) at amino acid position 5 to be replaced by a serine (S). 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

0.068

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.78

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.80

PhyloP100

0.15

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.11

REVEL

Benign

0.032

Sift

Benign

0.10

Sift4G

Uncertain

0.038

Polyphen

0.0

Vest4

0.058

MutPred

0.29

Gain of glycosylation at P5 (P = 0.0423);

MVP

0.64

MPC

0.74

ClinPred

0.19

GERP RS

2.8

PromoterAI

-0.072

Neutral

(source)

Varity_R

0.14

gMVP

0.22

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr2-46543059-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over