Variant 14-63205012-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020663.5(RHOJ):c.143A>T(p.Glu48Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,461,866 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: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RHOJ
NM_020663.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

Variant links:

Genes affected

RHOJ (HGNC:688): (ras homolog family member J) This gene encodes one of the many small GTP-binding proteins in the Rho family shown to be associated with focal adhesions in endothelial cells (PMID: 21148427, 22103495). The encoded protein is activated by vascular endothelial growth factor and may regulate angiogenesis. [provided by RefSeq, Dec 2011]

RHOJ links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2970779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RHOJ	NM_020663.5 linkuse as main transcript	c.143A>T	p.Glu48Val	missense_variant	1/5	ENST00000316754.8
RHOJ	XM_047431613.1 linkuse as main transcript	c.143A>T	p.Glu48Val	missense_variant	1/5
RHOJ	XM_011536993.4 linkuse as main transcript	c.143A>T	p.Glu48Val	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOJ	ENST00000316754.8 linkuse as main transcript	c.143A>T	p.Glu48Val	missense_variant	1/5	1	NM_020663.5	P1	Q9H4E5-1
RHOJ	ENST00000555125.1 linkuse as main transcript	c.143A>T	p.Glu48Val	missense_variant	1/4	2
RHOJ	ENST00000557133.1 linkuse as main transcript	n.328A>T		non_coding_transcript_exon_variant	1/2	2
RHOJ	ENST00000557447.5 linkuse as main transcript	c.143A>T	p.Glu48Val	missense_variant, NMD_transcript_variant	1/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250748

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135592

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:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727232

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:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

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

Jan 16, 2024

The c.143A>T (p.E48V) alteration is located in exon 1 (coding exon 1) of the RHOJ gene. This alteration results from a A to T substitution at nucleotide position 143, causing the glutamic acid (E) at amino acid position 48 to be replaced by a valine (V). 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

0.61

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.66

D;.

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.30

T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.57

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.22

T;T

Polyphen

0.23

B;.

Vest4

0.41

MutPred

0.43

Gain of catalytic residue at A45 (P = 0.0082);Gain of catalytic residue at A45 (P = 0.0082);

MVP

0.86

MPC

0.26

ClinPred

0.23

GERP RS

4.4

Varity_R

0.30

gMVP

0.63

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