Variant chrX-131088720-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144967.4(ARHGAP36):c.1579C>A(p.Arg527Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,210,067 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 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. R527C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Consequence

ARHGAP36
NM_144967.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.204

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0698944).

BS2

High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARHGAP36	NM_144967.4 linkuse as main transcript	c.1579C>A	p.Arg527Ser	missense_variant	12/12	ENST00000276211.10
ARHGAP36	NM_001282607.2 linkuse as main transcript	c.1543C>A	p.Arg515Ser	missense_variant	12/12
ARHGAP36	NM_001330651.1 linkuse as main transcript	c.1171C>A	p.Arg391Ser	missense_variant	11/11
ARHGAP36	XM_011531280.2 linkuse as main transcript	c.1171C>A	p.Arg391Ser	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP36	ENST00000276211.10 linkuse as main transcript	c.1579C>A	p.Arg527Ser	missense_variant	12/12	2	NM_144967.4	P4	Q6ZRI8-1

Frequencies

GnomAD3 genomes

AF:

0.0000534

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34498

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:

0.0000939

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000274

AC:

AN:

182217

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66709

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:

0.0000614

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1097711

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363081

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:

0.0000261

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000534

AC:

AN:

112356

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34498

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:

0.0000939

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000594

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

Mar 03, 2022

The c.1579C>A (p.R527S) alteration is located in exon 12 (coding exon 11) of the ARHGAP36 gene. This alteration results from a C to A substitution at nucleotide position 1579, causing the arginine (R) at amino acid position 527 to be replaced by a serine (S). 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

0.22

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;.;.;.;.

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.69

T;T;T;T;.

M_CAP

Benign

0.0062

MetaRNN

Benign

0.070

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.;.;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.61

N;N;.;N;N

REVEL

Benign

0.037

Sift

Benign

0.096

T;T;.;T;T

Sift4G

Benign

0.18

T;T;.;.;T

Polyphen

0.22

B;P;.;B;.

Vest4

0.15

MutPred

0.23

Gain of glycosylation at R527 (P = 0.0252);.;.;.;.;

MVP

0.12

MPC

0.68

ClinPred

0.12

GERP RS

2.5

Varity_R

0.17

gMVP

0.42

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