11-128969103-T-C

Variant names:

• chr11-128969103-T-C
• rs781418129
• NM_001378024.1:c.6110A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001378024.1(ARHGAP32):​c.6110A>G​(p.Tyr2037Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000997 in 1,605,536 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ARHGAP32 NM_001378024.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 15 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP32	NM_001378024.1	MANE Select	c.6110A>G	p.Tyr2037Cys	missense	Exon 23 of 23	NP_001364953.1	A0A804HK06
	ARHGAP32	NM_001142685.2		c.6068A>G	p.Tyr2023Cys	missense	Exon 22 of 22	NP_001136157.1	A7KAX9-1
	ARHGAP32	NM_001378025.1		c.5948A>G	p.Tyr1983Cys	missense	Exon 22 of 22	NP_001364954.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP32	ENST00000682385.1	MANE Select	c.6110A>G	p.Tyr2037Cys	missense	Exon 23 of 23	ENSP00000507720.1	A0A804HK06
	ARHGAP32	ENST00000310343.13	TSL:1	c.6068A>G	p.Tyr2023Cys	missense	Exon 22 of 22	ENSP00000310561.8	A7KAX9-1
	ARHGAP32	ENST00000392657.7	TSL:1	c.5021A>G	p.Tyr1674Cys	missense	Exon 13 of 13	ENSP00000376425.3	A7KAX9-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000809 AC: 2 AN: 247356 AF XY: 0.00000749

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1453330 Hom.: 0 Cov.: 30 AF XY: 0.00000970 AC XY: 7 AN XY: 721392

African (AFR) AF: 0.0000300 AC: 1 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25748

East Asian (EAS) AF: 0.00 AC: 0 AN: 39496

South Asian (SAS) AF: 0.00 AC: 0 AN: 85304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1106112

Other (OTH) AF: 0.0000167 AC: 1 AN: 59950

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.36		Loss of phosphorylation at Y2023 (P = 0.0078)
MVP		0.16
MPC		0.52
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.58
gMVP		0.44
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs781418129; hg19: chr11-128838998;