Variant 1-112703769-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_175744.5(RHOC):c.31G>A(p.Val11Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,266 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

RHOC
NM_175744.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

RHOC (HGNC:669): (ras homolog family member C) 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 protein encoded by this gene is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

RHOC links:

ENSG00000271810 (HGNC:):

ENSG00000271810 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOC	NM_175744.5 link	c.31G>A	p.Val11Ile	missense_variant	3/6	ENST00000339083.12	NP_786886.1	P08134A0A024R0C8
RHOC	NM_001042678.2 link	c.31G>A	p.Val11Ile	missense_variant	2/5		NP_001036143.1	P08134A0A024R0C8
RHOC	NM_001042679.2 link	c.31G>A	p.Val11Ile	missense_variant	3/6		NP_001036144.1	P08134A0A024R0C8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOC	ENST00000339083.12 link	c.31G>A	p.Val11Ile	missense_variant	3/6	1	NM_175744.5	ENSP00000345236.8		P08134
ENSG00000271810	ENST00000606505.5 link	c.520G>A	p.Val174Ile	missense_variant	6/8	5		ENSP00000476252.1		U3KQV3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247382

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133446

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460266

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726140

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

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 25, 2024

The c.31G>A (p.V11I) alteration is located in exon 3 (coding exon 1) of the RHOC gene. This alteration results from a G to A substitution at nucleotide position 31, causing the valine (V) at amino acid position 11 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

0.73

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;T;T;T;T;.;T;T;T;T;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

.;D;.;.;.;.;D;.;D;D;D;D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.74

D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.97

L;L;L;L;L;L;.;L;.;.;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.91

N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.093

T;T;T;T;T;T;T;T;.;.;.;.;.

Polyphen

0.94

P;P;P;P;P;P;.;P;.;.;.;.;.

Vest4

0.69

MutPred

0.67

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);

MVP

0.74

MPC

1.3

ClinPred

0.77

GERP RS

5.3

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.53

gMVP

0.55

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