14-63204876-T-C

Position:

• chr14-63204876-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_020663.5(RHOJ):​c.7T>C​(p.Cys3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RHOJ NM_020663.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.651

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a lipid_moiety_binding_region S-palmitoyl cysteine (size 0) in uniprot entity RHOJ_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104184926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOJ	NM_020663.5	c.7T>C	p.Cys3Arg	missense_variant	1/5	ENST00000316754.8	NP_065714.1
RHOJ	XM_047431613.1	c.7T>C	p.Cys3Arg	missense_variant	1/5		XP_047287569.1
RHOJ	XM_011536993.4	c.7T>C	p.Cys3Arg	missense_variant	1/4		XP_011535295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOJ	ENST00000316754.8	c.7T>C	p.Cys3Arg	missense_variant	1/5	1	NM_020663.5	ENSP00000316729.3
RHOJ	ENST00000555125.1	c.7T>C	p.Cys3Arg	missense_variant	1/4	2		ENSP00000451643.1
RHOJ	ENST00000557133.1	n.192T>C		non_coding_transcript_exon_variant	1/2	2
RHOJ	ENST00000557447.5	n.7T>C		non_coding_transcript_exon_variant	1/5	5		ENSP00000451796.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726538

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 21, 2024

The c.7T>C (p.C3R) alteration is located in exon 1 (coding exon 1) of the RHOJ gene. This alteration results from a T to C substitution at nucleotide position 7, causing the cysteine (C) at amino acid position 3 to be replaced by an arginine (R). 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	0.085
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.20	N;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.088
Sift	Benign	0.042	D;T
Sift4G	Uncertain	0.019	D;D
Polyphen		0.0010	B;.
Vest4		0.41
MutPred		0.25		Loss of methylation at K4 (P = 0.0491);Loss of methylation at K4 (P = 0.0491);
MVP		0.47
MPC		0.26
ClinPred		0.38	T
GERP RS		2.0
Varity_R		0.44
gMVP		0.69

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: chr14-63671594;