11-128969103-T-G

Variant names:

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

Variant summary

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

The NM_001378024.1(ARHGAP32):​c.6110A>C​(p.Tyr2037Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Y2037C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP32 NM_001378024.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Tyr2037Ser	missense	Exon 23 of 23	NP_001364953.1	A0A804HK06
	ARHGAP32	NM_001142685.2		c.6068A>C	p.Tyr2023Ser	missense	Exon 22 of 22	NP_001136157.1	A7KAX9-1
	ARHGAP32	NM_001378025.1		c.5948A>C	p.Tyr1983Ser	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>C	p.Tyr2037Ser	missense	Exon 23 of 23	ENSP00000507720.1	A0A804HK06
	ARHGAP32	ENST00000310343.13	TSL:1	c.6068A>C	p.Tyr2023Ser	missense	Exon 22 of 22	ENSP00000310561.8	A7KAX9-1
	ARHGAP32	ENST00000392657.7	TSL:1	c.5021A>C	p.Tyr1674Ser	missense	Exon 13 of 13	ENSP00000376425.3	A7KAX9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.32
Sift	Benign	0.060	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.77
MutPred		0.41		Gain of disorder (P = 0.0056)
MVP		0.23
MPC		0.27
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.66
gMVP		0.50
Mutation Taster		=66/34	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;