Genetic Variant ARHGAP23:p.Arg237Cys (chr17-38466392-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001199417.2(ARHGAP23):c.709C>T(p.Arg237Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,534,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ARHGAP23
NM_001199417.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.220

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053435445).

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.709C>T	p.Arg237Cys	missense	Exon 7 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.709C>T	p.Arg237Cys	missense	Exon 7 of 24	ENSP00000481862.1	Q9P227-1
ARHGAP23	ENST00000616767.2	TSL:3	c.1051C>T	p.Arg351Cys	missense	Exon 7 of 24	ENSP00000516485.1	A0A9L9PXS4
ARHGAP23	ENST00000633445.2	TSL:3	c.655C>T	p.Arg219Cys	missense	Exon 7 of 24	ENSP00000516484.1	A0A9L9PXQ2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000425

AC:

AN:

141058

AF XY:

0.0000264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000415

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000931

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1382434

Hom.:

Cov.:

AF XY:

0.0000352

AC XY:

AN XY:

681470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31440

American (AMR)

AF:

0.0000569

AC:

AN:

35178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24766

East Asian (EAS)

AF:

0.00

AC:

AN:

35584

South Asian (SAS)

AF:

0.000178

AC:

AN:

78652

European-Finnish (FIN)

AF:

0.0000255

AC:

AN:

39230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1074330

Other (OTH)

AF:

0.000104

AC:

AN:

57588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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

AF:

0.0000197

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000592

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.13

M_CAP

Benign

0.027

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.22

PrimateAI

Uncertain

0.67

Sift4G

Benign

0.061

Polyphen

0.0030

Vest4

0.11

MVP

0.35

ClinPred

0.031

GERP RS

2.0

Varity_R

0.18

gMVP

0.34

Mutation Taster

=93/7

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over