11-120429773-C-T

Variant names:

• chr11-120429773-C-T
• rs1172255122
• NM_015313.3:c.725C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015313.3(ARHGEF12):​c.725C>T​(p.Ala242Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000287 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: ARHGEF12 NM_015313.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19736046).
• BS2: High AC in GnomAdExome4 at 42 AD gene.

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.725C>T	p.Ala242Val	missense	Exon 10 of 41	NP_056128.1	Q9NZN5-1
	ARHGEF12	NM_001198665.2		c.668C>T	p.Ala223Val	missense	Exon 9 of 40	NP_001185594.1	Q9NZN5-2
	ARHGEF12	NM_001301084.2		c.416C>T	p.Ala139Val	missense	Exon 10 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.725C>T	p.Ala242Val	missense	Exon 10 of 41	ENSP00000380942.2	Q9NZN5-1
	ARHGEF12	ENST00000532993.5	TSL:1	c.416C>T	p.Ala139Val	missense	Exon 10 of 41	ENSP00000432984.1	E9PMR6
	ARHGEF12	ENST00000356641.7	TSL:5	c.668C>T	p.Ala223Val	missense	Exon 9 of 40	ENSP00000349056.3	Q9NZN5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249190 AF XY: 0.0000148

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461590 Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26 AN XY: 727082

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111834

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	0.020
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.6
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.060
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.017	D
Polyphen		0.12	B
Vest4		0.26
MutPred		0.15		Gain of methylation at K243 (P = 0.0378)
MVP		0.64
MPC		0.56
ClinPred		0.67	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.53
Mutation Taster		=73/27	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

dbSNP: rs1172255122; hg19: chr11-120300482;