rs1669121312

Variant names:

• chr2-46576219-C-G
• rs1669121312
• NM_012249.4:c.334C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-46576219-C-G
• chr2-46576219-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012249.4(RHOQ):​c.334C>G​(p.Pro112Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHOQ NM_012249.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012249.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOQ	NM_012249.4	MANE Select	c.334C>G	p.Pro112Ala	missense	Exon 3 of 5	NP_036381.2	P17081
	RHOQ-AS1	NR_104182.1		n.204+3816G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOQ	ENST00000238738.9	TSL:1 MANE Select	c.334C>G	p.Pro112Ala	missense	Exon 3 of 5	ENSP00000238738.4	P17081
	RHOQ-AS1	ENST00000506009.3	TSL:1	n.214+3816G>C		intron	N/A
	RHOQ	ENST00000945010.1		c.196C>G	p.Pro66Ala	missense	Exon 2 of 4	ENSP00000615069.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.70
MutPred		0.63		Loss of stability (P = 0.0389)
MVP		0.95
MPC		1.7
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.76
gMVP		0.60
Mutation Taster		=42/58	disease causing

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

Other links and lift over

dbSNP: rs1669121312; hg19: chr2-46803358;