11-128968948-A-C

Variant names:

• chr11-128968948-A-C
• rs1445909124
• NM_001378024.1:c.6265T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378024.1(ARHGAP32):​c.6265T>G​(p.Leu2089Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,406,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L2089M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ARHGAP32 NM_001378024.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26226944).

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.6265T>G	p.Leu2089Val	missense	Exon 23 of 23	NP_001364953.1	A0A804HK06
	ARHGAP32	NM_001142685.2		c.6223T>G	p.Leu2075Val	missense	Exon 22 of 22	NP_001136157.1	A7KAX9-1
	ARHGAP32	NM_001378025.1		c.6103T>G	p.Leu2035Val	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.6265T>G	p.Leu2089Val	missense	Exon 23 of 23	ENSP00000507720.1	A0A804HK06
	ARHGAP32	ENST00000310343.13	TSL:1	c.6223T>G	p.Leu2075Val	missense	Exon 22 of 22	ENSP00000310561.8	A7KAX9-1
	ARHGAP32	ENST00000392657.7	TSL:1	c.5176T>G	p.Leu1726Val	missense	Exon 13 of 13	ENSP00000376425.3	A7KAX9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000461 AC: 1 AN: 217128 AF XY: 0.00

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: 0.0000517

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1406310 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691516

African (AFR) AF: 0.00 AC: 0 AN: 32184

American (AMR) AF: 0.00 AC: 0 AN: 39562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23324

East Asian (EAS) AF: 0.00 AC: 0 AN: 38834

South Asian (SAS) AF: 0.00 AC: 0 AN: 78352

European-Finnish (FIN) AF: 0.0000770 AC: 4 AN: 51934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080014

Other (OTH) AF: 0.00 AC: 0 AN: 57818

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.91
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.91	P
Vest4		0.49
MutPred		0.24		Gain of sheet (P = 0.0101)
MVP		0.17
MPC		0.57
ClinPred		0.45	T
GERP RS		-11
Varity_R		0.19
gMVP		0.37
Mutation Taster		=84/16	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: rs1445909124; hg19: chr11-128838843;