dbSNP rs375908303: RHOQ:p.Met80Lys (chr2-46576124-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012249.4(RHOQ):c.239T>A(p.Met80Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. M80T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RHOQ
NM_012249.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.01

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:

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

RHOQ-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOQ	NM_012249.4 link	c.239T>A	p.Met80Lys	missense_variant	Exon 3 of 5	ENST00000238738.9	NP_036381.2	P17081V9HWD0
RHOQ	XM_011532726.3 link	c.239T>A	p.Met80Lys	missense_variant	Exon 3 of 6		XP_011531028.1
RHOQ-AS1	NR_104182.1 link	n.204+3911A>T		intron_variant	Intron 1 of 1
RHOQ	XM_005264229.3 link	c.202-4804T>A		intron_variant	Intron 2 of 2		XP_005264286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOQ	ENST00000238738.9 link	c.239T>A	p.Met80Lys	missense_variant	Exon 3 of 5	1	NM_012249.4	ENSP00000238738.4		P17081

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1460376

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

44348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111340

Other (OTH)

AF:

0.00

AC:

AN:

60340

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.28

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.057

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.058

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-2.1

N;.

PhyloP100

4.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.098

T;D

Polyphen

0.012

B;.

Vest4

0.73

MutPred

0.50

Gain of ubiquitination at M80 (P = 0.0388);.;

MVP

0.85

MPC

1.1

ClinPred

0.83

GERP RS

5.4

Varity_R

0.90

gMVP

0.87

Mutation Taster

=58/42

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

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rs375908303

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over