Genetic Variant NM_001378024.1:c.6172G>A (chr11-128969041-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3042220.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 196 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378024.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP32	NM_001378024.1	MANE Select	c.6172G>A	p.Gly2058Ser	missense	Exon 23 of 23	NP_001364953.1	A0A804HK06
ARHGAP32	NM_001142685.2		c.6130G>A	p.Gly2044Ser	missense	Exon 22 of 22	NP_001136157.1	A7KAX9-1
ARHGAP32	NM_001378025.1		c.6010G>A	p.Gly2004Ser	missense	Exon 22 of 22	NP_001364954.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP32	ENST00000682385.1	MANE Select	c.6172G>A	p.Gly2058Ser	missense	Exon 23 of 23	ENSP00000507720.1	A0A804HK06
ARHGAP32	ENST00000310343.13	TSL:1	c.6130G>A	p.Gly2044Ser	missense	Exon 22 of 22	ENSP00000310561.8	A7KAX9-1
ARHGAP32	ENST00000392657.7	TSL:1	c.5083G>A	p.Gly1695Ser	missense	Exon 13 of 13	ENSP00000376425.3	A7KAX9-2

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

GnomAD2 exomes

AF:

0.00107

AC:

268

AN:

250302

AF XY:

0.00120

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 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

African (AFR)

AF:

0.000269

AC:

AN:

33452

American (AMR)

AF:

0.000740

AC:

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.000151

AC:

AN:

86060

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00259

AC:

2874

AN:

1110742

Other (OTH)

AF:

0.00153

AC:

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

187

374

560

747

934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.00129

AC:

196

AN:

152282

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41568

American (AMR)

AF:

0.00235

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00207

AC:

141

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.00165

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARHGAP32-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.20

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.081

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.45

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.1

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.69

REVEL

Benign

0.037

Sift

Benign

0.043

Sift4G

Benign

0.087

Polyphen

0.0040

Vest4

0.14

MVP

0.082

MPC

0.15

ClinPred

0.016

GERP RS

0.60

Varity_R

0.029

gMVP

0.19

Mutation Taster

=100/0

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