Genetic Variant ARHGAP23:p.Arg89Gly (chr17-38462857-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001199417.2(ARHGAP23):c.265C>G(p.Arg89Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 1,368,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R89W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ARHGAP23
NM_001199417.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.22

Publications

0 publications found

Variant links:

Genes affected

ARHGAP23 (HGNC:29293): (Rho GTPase activating protein 23) The RHO (see ARHA; MIM 165390) family of small GTPases are involved in signal transduction through transmembrane receptors, and they are inactive in the GDP-bound form and active in the GTP-bound form. GTPase-activating proteins, such as ARHGAP23, inactivate RHO family proteins by stimulating their hydrolysis of GTP (Katoh and Katoh, 2004 [PubMed 15254754]).[supplied by OMIM, Mar 2008]

ARHGAP23 links:

ENSG00000276170 (HGNC:):

ENSG00000276170 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2959637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199417.2. 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
	ARHGAP23	NM_001199417.2	MANE Select	c.265C>G	p.Arg89Gly	missense	Exon 4 of 24	NP_001186346.1	Q9P227-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP23	ENST00000622683.5	TSL:5 MANE Select	c.265C>G	p.Arg89Gly	missense	Exon 4 of 24	ENSP00000481862.1	Q9P227-1
ARHGAP23	ENST00000616767.2	TSL:3	c.607C>G	p.Arg203Gly	missense	Exon 4 of 24	ENSP00000516485.1	A0A9L9PXS4
ARHGAP23	ENST00000633445.2	TSL:3	c.211C>G	p.Arg71Gly	missense	Exon 4 of 24	ENSP00000516484.1	A0A9L9PXQ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

128724

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1368928

Hom.:

Cov.:

AF XY:

0.0000178

AC XY:

AN XY:

674024

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29506

American (AMR)

AF:

0.00

AC:

AN:

25824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23862

East Asian (EAS)

AF:

0.00

AC:

AN:

35394

South Asian (SAS)

AF:

0.00

AC:

AN:

74504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

1068548

Other (OTH)

AF:

0.00

AC:

AN:

56640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.072

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.78

PhyloP100

6.2

PrimateAI

Uncertain

0.61

Sift4G

Uncertain

0.0050

Vest4

0.53

MVP

0.51

ClinPred

0.96

GERP RS

5.2

Varity_R

0.37

gMVP

0.64

Mutation Taster

=288/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over