Variant 1-228735863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021205.6(RHOU):c.121C>T(p.Arg41Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000666 in 1,410,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

RHOU
NM_021205.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.315

Variant links:

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 links:

RHOU (HGNC:):

RHOU links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25190097).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOU	NM_021205.6 linkuse as main transcript	c.121C>T	p.Arg41Cys	missense_variant	1/3	ENST00000366691.4	NP_067028.1	Q7L0Q8-1A0A024R3Q7
RHOU	NR_037962.1 linkuse as main transcript	n.387-1810C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOU	ENST00000366691.4 linkuse as main transcript	c.121C>T	p.Arg41Cys	missense_variant	1/3	1	NM_021205.6	ENSP00000355652.3		Q7L0Q8-1

Frequencies

GnomAD3 genomes

AF:

0.0000925

AC:

AN:

151420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.000963

GnomAD3 exomes

AF:

0.0000145

AC:

AN:

68774

Hom.:

AF XY:

0.0000258

AC XY:

AN XY:

38826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000338

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000635

AC:

AN:

1258978

Hom.:

Cov.:

AF XY:

0.0000647

AC XY:

AN XY:

618148

show subpopulations

Gnomad4 AFR exome

AF:

0.000946

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000492

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000326

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.0000924

AC:

AN:

151528

Hom.:

Cov.:

AF XY:

0.0000945

AC XY:

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.000953

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.0000272

AC:

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

Aug 30, 2021

The c.121C>T (p.R41C) alteration is located in exon 1 (coding exon 1) of the RHOU gene. This alteration results from a C to T substitution at nucleotide position 121, causing the arginine (R) at amino acid position 41 to be replaced by a cysteine (C). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.32

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.040

REVEL

Benign

0.15

Sift

Uncertain

0.0030

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.12

MutPred

0.45

Loss of methylation at R41 (P = 0.0039);

MVP

0.22

MPC

3.2

ClinPred

0.22

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.15

gMVP

0.62

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