1-228735899-G-C

Position:

• chr1-228735899-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021205.6(RHOU):​c.157G>C​(p.Val53Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHOU NM_021205.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07

Genes affected

RHOU (HGNC:17794): (ras homolog family member U) This gene encodes a member of the Rho family of GTPases. This protein can activate PAK1 and JNK1, and can induce filopodium formation and stress fiber dissolution. It may also mediate the effects of WNT1 signaling in the regulation of cell morphology, cytoskeletal organization, and cell proliferation. A non-coding transcript variant of this gene results from naturally occurring read-through transcription between this locus and the neighboring DUSP5P (dual specificity phosphatase 5 pseudogene) locus.[provided by RefSeq, Mar 2011]

RHOU (HGNC:):

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/exons	MANE	Protein	UniProt
RHOU	NM_021205.6	c.157G>C	p.Val53Leu	missense_variant	1/3	ENST00000366691.4	NP_067028.1
RHOU	NR_037962.1	n.387-1774G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOU	ENST00000366691.4	c.157G>C	p.Val53Leu	missense_variant	1/3	1	NM_021205.6	ENSP00000355652.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.157G>C (p.V53L) alteration is located in exon 1 (coding exon 1) of the RHOU gene. This alteration results from a G to C substitution at nucleotide position 157, causing the valine (V) at amino acid position 53 to be replaced by a leucine (L). 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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.015
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.067	B
Vest4		0.50
MutPred		0.74		Gain of catalytic residue at V53 (P = 0.0159);
MVP		0.64
MPC		0.42
ClinPred		0.93	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.91
gMVP		0.80

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: chr1-228871646;