Variant 11-128969041-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001378024.1(ARHGAP32):c.6172G>A(p.Gly2058Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,612,246 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 7 hom. )

Consequence

ARHGAP32
NM_001378024.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

ARHGAP32 (HGNC:17399): (Rho GTPase activating protein 32) RICS is a neuron-associated GTPase-activating protein that may regulate dendritic spine morphology and strength by modulating Rho GTPase (see RHOA; MIM 165390) activity (Okabe et al., 2003 [PubMed 12531901]).[supplied by OMIM, Mar 2008]

ARHGAP32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004345149).

BP6

Variant 11-128969041-C-T is Benign according to our data. Variant chr11-128969041-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042220.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 196 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP32	NM_001378024.1 linkuse as main transcript	c.6172G>A	p.Gly2058Ser	missense_variant	23/23	ENST00000682385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP32	ENST00000682385.1 linkuse as main transcript	c.6172G>A	p.Gly2058Ser	missense_variant	23/23		NM_001378024.1	P3

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00107

AC:

268

AN:

250302

Hom.:

AF XY:

0.00120

AC XY:

162

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00199

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00207

AC:

3029

AN:

1459964

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

1476

AN XY:

725888

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000740

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00259

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00129

AC:

196

AN:

152282

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00135

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00113

AC:

137

EpiCase

AF:

0.00229

EpiControl

AF:

0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARHGAP32-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 17, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.20

DANN

Benign

0.72

DEOGEN2

Benign

0.081

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.45

T;.;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.69

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.043

D;D;D

Sift4G

Benign

0.087

T;T;T

Polyphen

0.0040

B;.;.

Vest4

0.14

MVP

0.082

MPC

0.15

ClinPred

0.016

GERP RS

0.60

Varity_R

0.029

gMVP

0.19

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