Variant 1-228735951-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_021205.6(RHOU):c.209C>T(p.Thr70Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,430,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RHOU
NM_021205.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOU	NM_021205.6 linkuse as main transcript	c.209C>T	p.Thr70Ile	missense_variant	1/3	ENST00000366691.4	NP_067028.1	Q7L0Q8-1A0A024R3Q7
RHOU	NR_037962.1 linkuse as main transcript	n.387-1722C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOU	ENST00000366691.4 linkuse as main transcript	c.209C>T	p.Thr70Ile	missense_variant	1/3	1	NM_021205.6	ENSP00000355652.3		Q7L0Q8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712524

show subpopulations

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:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 06, 2021

The c.209C>T (p.T70I) 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 209, causing the threonine (T) at amino acid position 70 to be replaced by an isoleucine (I). 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

0.96

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.098

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.56

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.52

Sift

Benign

0.041

Sift4G

Uncertain

0.053

Polyphen

0.31

Vest4

0.56

MutPred

0.81

Loss of glycosylation at T70 (P = 0.0587);

MVP

0.30

MPC

0.70

ClinPred

0.99

GERP RS

3.7

Varity_R

0.71

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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