Genetic Variant NM_001378024.1:c.6073G>A (chr11-128969140-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001378024.1(ARHGAP32):c.6073G>A(p.Gly2025Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,455,124 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

ARHGAP32
NM_001378024.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.782

Publications

0 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04421848).

BS2

High AC in GnomAdExome4 at 20 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.6073G>A	p.Gly2025Ser	missense	Exon 23 of 23	NP_001364953.1	A0A804HK06
ARHGAP32	NM_001142685.2		c.6031G>A	p.Gly2011Ser	missense	Exon 22 of 22	NP_001136157.1	A7KAX9-1
ARHGAP32	NM_001378025.1		c.5911G>A	p.Gly1971Ser	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.6073G>A	p.Gly2025Ser	missense	Exon 23 of 23	ENSP00000507720.1	A0A804HK06
ARHGAP32	ENST00000310343.13	TSL:1	c.6031G>A	p.Gly2011Ser	missense	Exon 22 of 22	ENSP00000310561.8	A7KAX9-1
ARHGAP32	ENST00000392657.7	TSL:1	c.4984G>A	p.Gly1662Ser	missense	Exon 13 of 13	ENSP00000376425.3	A7KAX9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000403

AC:

AN:

248284

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1455124

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722592

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.000315

AC:

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25802

East Asian (EAS)

AF:

0.00

AC:

AN:

39534

South Asian (SAS)

AF:

0.00

AC:

AN:

85452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000452

AC:

AN:

1107384

Other (OTH)

AF:

0.0000167

AC:

AN:

60056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.6

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.13

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.79

M_CAP

Benign

0.012

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.78

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

REVEL

Benign

0.026

Sift

Benign

0.33

Sift4G

Benign

0.20

Polyphen

0.20

Vest4

0.17

MutPred

0.12

Gain of glycosylation at G2011 (P = 0.069)

MVP

0.11

MPC

0.13

ClinPred

0.046

GERP RS

1.3

Varity_R

0.035

gMVP

0.17

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over