Genetic Variant ARHGAP36:p.Ala200Val (chrX-131084258-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_144967.4(ARHGAP36):c.599C>T(p.Ala200Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000505 in 1,208,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A200D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000054 ( 0 hom. 17 hem. )

Consequence

ARHGAP36
NM_144967.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Publications

0 publications found

Variant links:

Genes affected

ARHGAP36 (HGNC:26388): (Rho GTPase activating protein 36) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP36 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 17 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP36	NM_144967.4	MANE Select	c.599C>T	p.Ala200Val	missense	Exon 5 of 12	NP_659404.2
ARHGAP36	NM_001282607.2		c.563C>T	p.Ala188Val	missense	Exon 5 of 12	NP_001269536.1	Q6ZRI8-4
ARHGAP36	NM_001330651.1		c.191C>T	p.Ala64Val	missense	Exon 4 of 11	NP_001317580.1	Q6ZRI8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP36	ENST00000276211.10	TSL:2 MANE Select	c.599C>T	p.Ala200Val	missense	Exon 5 of 12	ENSP00000276211.5	Q6ZRI8-1
ARHGAP36	ENST00000370922.5	TSL:1	c.563C>T	p.Ala188Val	missense	Exon 5 of 12	ENSP00000359960.1	Q6ZRI8-4
ARHGAP36	ENST00000412432.6	TSL:1	c.506C>T	p.Ala169Val	missense	Exon 5 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000335

AC:

AN:

179224

AF XY:

0.00

show subpopulations

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:

0.0000746

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000538

AC:

AN:

1096378

Hom.:

Cov.:

AF XY:

0.0000470

AC XY:

AN XY:

361926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26321

American (AMR)

AF:

0.00

AC:

AN:

34951

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19270

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

53604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4102

European-Non Finnish (NFE)

AF:

0.0000666

AC:

AN:

841421

Other (OTH)

AF:

0.0000652

AC:

AN:

46018

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

Exome Hom

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:

0.0000178

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34526

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30854

American (AMR)

AF:

0.00

AC:

AN:

10720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3567

South Asian (SAS)

AF:

0.00

AC:

AN:

2694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6161

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53286

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00000378

ExAC

AF:

0.0000247

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

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.86

M_CAP

Benign

0.0095

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

5.1

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.21

Sift

Benign

0.12

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.20

MutPred

0.74

Loss of disorder (P = 0.086)

MVP

0.21

MPC

0.64

ClinPred

0.50

GERP RS

5.0

Varity_R

0.12

gMVP

0.82

Mutation Taster

=77/23

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