Variant chrX-131084258-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARHGAP36	NM_144967.4 linkuse as main transcript	c.599C>T	p.Ala200Val	missense_variant	5/12	ENST00000276211.10
ARHGAP36	NM_001282607.2 linkuse as main transcript	c.563C>T	p.Ala188Val	missense_variant	5/12
ARHGAP36	NM_001330651.1 linkuse as main transcript	c.191C>T	p.Ala64Val	missense_variant	4/11
ARHGAP36	XM_011531280.2 linkuse as main transcript	c.191C>T	p.Ala64Val	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP36	ENST00000276211.10 linkuse as main transcript	c.599C>T	p.Ala200Val	missense_variant	5/12	2	NM_144967.4	P4	Q6ZRI8-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34526

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

GnomAD3 exomes

AF:

0.0000335

AC:

AN:

179224

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63888

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 SAS 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

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:

0.0000666

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34526

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

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 08, 2024

The c.599C>T (p.A200V) alteration is located in exon 5 (coding exon 4) of the ARHGAP36 gene. This alteration results from a C to T substitution at nucleotide position 599, causing the alanine (A) at amino acid position 200 to be replaced by a valine (V). 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

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

T;.;.;.;.;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.86

D;D;D;D;D;.

M_CAP

Benign

0.0095

MetaRNN

Uncertain

0.60

D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.6

D;D;D;.;D;D

REVEL

Benign

0.21

Sift

Benign

0.12

T;D;D;.;D;D

Sift4G

Uncertain

0.024

D;D;D;.;.;D

Polyphen

1.0

D;D;.;.;D;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over