14-63204886-G-A

Position:

• chr14-63204886-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020663.5(RHOJ):​c.17G>A​(p.Gly6Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHOJ NM_020663.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05990976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOJ	NM_020663.5	c.17G>A	p.Gly6Glu	missense_variant	1/5	ENST00000316754.8	NP_065714.1
RHOJ	XM_047431613.1	c.17G>A	p.Gly6Glu	missense_variant	1/5		XP_047287569.1
RHOJ	XM_011536993.4	c.17G>A	p.Gly6Glu	missense_variant	1/4		XP_011535295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOJ	ENST00000316754.8	c.17G>A	p.Gly6Glu	missense_variant	1/5	1	NM_020663.5	ENSP00000316729.3
RHOJ	ENST00000555125.1	c.17G>A	p.Gly6Glu	missense_variant	1/4	2		ENSP00000451643.1
RHOJ	ENST00000557133.1	n.202G>A		non_coding_transcript_exon_variant	1/2	2
RHOJ	ENST00000557447.5	n.17G>A		non_coding_transcript_exon_variant	1/5	5		ENSP00000451796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 23, 2023

The c.17G>A (p.G6E) alteration is located in exon 1 (coding exon 1) of the RHOJ gene. This alteration results from a G to A substitution at nucleotide position 17, causing the glycine (G) at amino acid position 6 to be replaced by a glutamic acid (E). 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	Benign	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.11
Sift	Benign	0.57	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.0	B;.
Vest4		0.049
MutPred		0.20		Gain of catalytic residue at M1 (P = 0);Gain of catalytic residue at M1 (P = 0);
MVP		0.70
MPC		0.17
ClinPred		0.090	T
GERP RS		2.5
Varity_R		0.030
gMVP		0.43

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: chr14-63671604;