Variant 11-120431886-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015313.3(ARHGEF12):c.899C>T(p.Ser300Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,400 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARHGEF12
NM_015313.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Variant links:

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]

ARHGEF12 links:

ARHGEF12 (HGNC:):

ARHGEF12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF12	NM_015313.3 linkuse as main transcript	c.899C>T	p.Ser300Phe	missense_variant	11/41	ENST00000397843.7	NP_056128.1	Q9NZN5-1B4E2K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGEF12	ENST00000397843.7 linkuse as main transcript	c.899C>T	p.Ser300Phe	missense_variant	11/41	1	NM_015313.3	ENSP00000380942.2	Q9NZN5-1
ARHGEF12	ENST00000532993.5 linkuse as main transcript	c.590C>T	p.Ser197Phe	missense_variant	11/41	1		ENSP00000432984.1	E9PMR6
ARHGEF12	ENST00000356641.7 linkuse as main transcript	c.842C>T	p.Ser281Phe	missense_variant	10/40	5		ENSP00000349056.3	Q9NZN5-2
ARHGEF12	ENST00000529970.5 linkuse as main transcript	n.1033C>T		non_coding_transcript_exon_variant	11/36	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458400

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725360

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 02, 2024

The c.899C>T (p.S300F) alteration is located in exon 11 (coding exon 11) of the ARHGEF12 gene. This alteration results from a C to T substitution at nucleotide position 899, causing the serine (S) at amino acid position 300 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.2

.;M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.035

D;D;D

Sift4G

Uncertain

0.047

D;D;T

Polyphen

0.98

D;D;.

Vest4

0.69

MutPred

0.28

.;Loss of phosphorylation at S300 (P = 0.0032);.;

MVP

0.76

MPC

0.65

ClinPred

0.94

GERP RS

5.5

Varity_R

0.16

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over