Variant X-131083880-C-G 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.466C>G(p.Arg156Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,210,707 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.00011 ( 0 hom. 41 hem. )

Consequence

ARHGAP36
NM_144967.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

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=0.17744243).

BS2

High Hemizygotes in GnomAdExome4 at 41 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARHGAP36	NM_144967.4 linkuse as main transcript	c.466C>G	p.Arg156Gly	missense_variant	4/12	ENST00000276211.10
ARHGAP36	NM_001282607.2 linkuse as main transcript	c.430C>G	p.Arg144Gly	missense_variant	4/12
ARHGAP36	NM_001330651.1 linkuse as main transcript	c.58C>G	p.Arg20Gly	missense_variant	3/11
ARHGAP36	XM_011531280.2 linkuse as main transcript	c.58C>G	p.Arg20Gly	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP36	ENST00000276211.10 linkuse as main transcript	c.466C>G	p.Arg156Gly	missense_variant	4/12	2	NM_144967.4	P4	Q6ZRI8-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34612

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

183419

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

67863

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:

0.0000733

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000115

AC:

126

AN:

1098243

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

363599

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34612

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000375

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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 17, 2023

The c.466C>G (p.R156G) alteration is located in exon 4 (coding exon 3) of the ARHGAP36 gene. This alteration results from a C to G substitution at nucleotide position 466, causing the arginine (R) at amino acid position 156 to be replaced by a glycine (G). 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

0.079

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

T;.;.;.;.;.

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

T;T;T;T;T;.

M_CAP

Benign

0.042

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.82

N;N;N;.;N;N

REVEL

Benign

0.076

Sift

Benign

0.14

T;T;T;.;T;D

Sift4G

Benign

0.13

T;T;D;.;.;T

Polyphen

0.0

B;B;.;.;B;.

Vest4

0.19

MVP

0.068

MPC

0.76

ClinPred

0.11

GERP RS

4.3

Varity_R

0.24

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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