11-128969315-C-A

Variant summary

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

The NM_001378024.1(ARHGAP32):​c.5898G>T​(p.Trp1966Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ARHGAP32
NM_001378024.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.244
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]

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=0.08702305).
BS2
High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARHGAP32NM_001378024.1 linkuse as main transcriptc.5898G>T p.Trp1966Cys missense_variant 23/23 ENST00000682385.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARHGAP32ENST00000682385.1 linkuse as main transcriptc.5898G>T p.Trp1966Cys missense_variant 23/23 NM_001378024.1 P3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251466
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727246
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:
0.0000198
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000555
Hom.:
0
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0

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 submitterclinical testingAmbry GeneticsDec 06, 2023The c.5856G>T (p.W1952C) alteration is located in exon 22 (coding exon 22) of the ARHGAP32 gene. This alteration results from a G to T substitution at nucleotide position 5856, causing the tryptophan (W) at amino acid position 1952 to be replaced by a cysteine (C). 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
0.17
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
14
DANN
Benign
0.88
DEOGEN2
Benign
0.080
T;.;.
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.84
T;.;T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.087
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.47
N;N;N
REVEL
Benign
0.10
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.048
D;D;D
Polyphen
0.56
P;.;.
Vest4
0.26
MutPred
0.28
Gain of catalytic residue at P1951 (P = 0.0086);.;.;
MVP
0.068
MPC
0.32
ClinPred
0.28
T
GERP RS
-5.5
Varity_R
0.095
gMVP
0.16

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.

Other links and lift over

dbSNP: rs771009084; hg19: chr11-128839210; API