chr2-46576621-A-G

Position:

chr2-46576621-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012249.4(RHOQ):c.427A>G(p.Ile143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000516 in 1,609,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RHOQ
NM_012249.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

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:

RHOQ-AS1 (HGNC:40816): (RHOQ antisense RNA 1)

RHOQ-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03909114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RHOQ	NM_012249.4 linkuse as main transcript	c.427A>G	p.Ile143Val	missense_variant	4/5	ENST00000238738.9	NP_036381.2
RHOQ-AS1	NR_104182.1 linkuse as main transcript	n.204+3414T>C		intron_variant, non_coding_transcript_variant
RHOQ	XM_011532726.3 linkuse as main transcript	c.427A>G	p.Ile143Val	missense_variant	4/6		XP_011531028.1
RHOQ	XM_005264229.3 linkuse as main transcript	c.202-4307A>G		intron_variant			XP_005264286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOQ	ENST00000238738.9 linkuse as main transcript	c.427A>G	p.Ile143Val	missense_variant	4/5	1	NM_012249.4	ENSP00000238738	P1
RHOQ-AS1	ENST00000506009.2 linkuse as main transcript	n.204+3414T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000685

AC:

AN:

248288

Hom.:

AF XY:

0.0000746

AC XY:

AN XY:

134090

show subpopulations

Gnomad AFR exome

AF:

0.000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1457460

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

725018

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000223

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000772

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.0000547

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 submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.427A>G (p.I143V) 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 427, causing the isoleucine (I) at amino acid position 143 to be replaced by a valine (V). 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

0.065

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.28

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.11

Sift

Benign

0.29

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0

B;.

Vest4

0.18

MVP

0.73

MPC

0.61

ClinPred

0.0082

GERP RS

1.9

Varity_R

0.036

gMVP

0.47

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