NM_015313.3:c.865C>G

Variant names:

• chr11-120431852-C-G
• NM_015313.3:c.865C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015313.3(ARHGEF12):​c.865C>G​(p.Leu289Val) 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. 15/22 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: ARHGEF12 NM_015313.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.796
• Publications: 0 publications found

Genes affected

ARHGEF12 (HGNC:14193): (Rho guanine nucleotide exchange factor 12) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086357296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015313.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF12	NM_015313.3	MANE Select	c.865C>G	p.Leu289Val	missense	Exon 11 of 41	NP_056128.1	Q9NZN5-1
	ARHGEF12	NM_001198665.2		c.808C>G	p.Leu270Val	missense	Exon 10 of 40	NP_001185594.1	Q9NZN5-2
	ARHGEF12	NM_001301084.2		c.556C>G	p.Leu186Val	missense	Exon 11 of 41	NP_001288013.1	E9PMR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF12	ENST00000397843.7	TSL:1 MANE Select	c.865C>G	p.Leu289Val	missense	Exon 11 of 41	ENSP00000380942.2	Q9NZN5-1
	ARHGEF12	ENST00000532993.5	TSL:1	c.556C>G	p.Leu186Val	missense	Exon 11 of 41	ENSP00000432984.1	E9PMR6
	ARHGEF12	ENST00000356641.7	TSL:5	c.808C>G	p.Leu270Val	missense	Exon 10 of 40	ENSP00000349056.3	Q9NZN5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.80
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.025
Sift	Benign	0.069	T
Sift4G	Benign	0.50	T
Polyphen		0.010	B
Vest4		0.059
MutPred		0.25		Loss of catalytic residue at L289 (P = 0.0756)
MVP		0.52
MPC		0.54
ClinPred		0.052	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.11
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr11-120302561;