Variant chr1-156939630-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198236.3(ARHGEF11):c.4014G>T(p.Trp1338Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARHGEF11
NM_198236.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

ARHGEF11 (HGNC:14580): (Rho guanine nucleotide exchange factor 11) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. A similar protein in rat interacts with glutamate transporter EAAT4 and modulates its glutamate transport activity. Expression of the rat protein induces the reorganization of the actin cytoskeleton and its overexpression induces the formation of membrane ruffling and filopodia. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ARHGEF11 links:

LRRC71 (HGNC:26556): (leucine rich repeat containing 71)

LRRC71 links:

ARHGEF11 (HGNC:):

ARHGEF11 links:

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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
ARHGEF11	NM_198236.3 linkuse as main transcript	c.4014G>T	p.Trp1338Cys	missense_variant	37/41	ENST00000368194.8	NP_937879.1	O15085-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGEF11	ENST00000368194.8 linkuse as main transcript	c.4014G>T	p.Trp1338Cys	missense_variant	37/41	1	NM_198236.3	ENSP00000357177.3	O15085-2
ARHGEF11	ENST00000361409.2 linkuse as main transcript	c.3894G>T	p.Trp1298Cys	missense_variant	36/40	1		ENSP00000354644.2	O15085-1
ARHGEF11	ENST00000487682.5 linkuse as main transcript	n.1932G>T		non_coding_transcript_exon_variant	7/10	2
ARHGEF11	ENST00000492592.1 linkuse as main transcript	n.111G>T		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727032

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:

8.99e-7

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

Jan 26, 2022

The c.3894G>T (p.W1298C) alteration is located in exon 36 (coding exon 36) of the ARHGEF11 gene. This alteration results from a G to T substitution at nucleotide position 3894, causing the tryptophan (W) at amino acid position 1298 to be replaced by a cysteine (C). 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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.1

.;L

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.057

T;T

Polyphen

1.0

D;D

Vest4

0.53

MutPred

0.27

.;Loss of catalytic residue at P1301 (P = 0.0262);

MVP

0.73

MPC

0.30

ClinPred

0.96

GERP RS

4.5

Varity_R

0.22

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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