rs375908303

Variant names:

• chr2-46576124-T-A
• NM_012249.4:c.239T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-46576124-T-A
• chr2-46576124-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

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

Verdict is Uncertain_significance. Variant got 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	c.239T>A	p.Met80Lys	missense_variant	Exon 3 of 5	ENST00000238738.9	NP_036381.2
RHOQ	XM_011532726.3	c.239T>A	p.Met80Lys	missense_variant	Exon 3 of 6		XP_011531028.1
RHOQ	XM_005264229.3	c.202-4804T>A		intron_variant	Intron 2 of 2		XP_005264286.1
RHOQ-AS1	NR_104182.1	n.204+3911A>T		intron_variant	Intron 1 of 1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460376 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726624

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: 9.00e-7

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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-2.1	N;.
PrimateAI	Pathogenic	0.86	D
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	D
GERP RS		5.4
Varity_R		0.90
gMVP		0.87

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: chr2-46803263;