Variant 12-57476372-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032496.4(ARHGAP9):c.1108T>G(p.Ser370Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,613,282 control chromosomes in the GnomAD database, including 286,440 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.47 ( 19470 hom., cov: 31)

Exomes 𝑓: 0.60 ( 266970 hom. )

Consequence

ARHGAP9
NM_032496.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.111

Variant links:

Genes affected

ARHGAP9 (HGNC:14130): (Rho GTPase activating protein 9) This gene encodes a member of the Rho-GAP family of GTPase activating proteins. The protein has substantial GAP activity towards several Rho-family GTPases in vitro, converting them to an inactive GDP-bound state. It is implicated in regulating adhesion of hematopoietic cells to the extracellular matrix. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ARHGAP9 links:

MARS1 (HGNC:6898): (methionyl-tRNA synthetase 1) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase complex and catalyzes the ligation of methionine to tRNA molecules. [provided by RefSeq, Jan 2011]

MARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7234335E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP9	NM_032496.4 linkuse as main transcript	c.1108T>G	p.Ser370Ala	missense_variant	8/18	ENST00000393791.8	NP_115885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP9	ENST00000393791.8 linkuse as main transcript	c.1108T>G	p.Ser370Ala	missense_variant	8/18	1	NM_032496.4	ENSP00000377380		Q9BRR9-2

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71421

AN:

151878

Hom.:

19481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.520

GnomAD3 exomes

AF:

0.504

AC:

126022

AN:

249864

Hom.:

34746

AF XY:

0.521

AC XY:

70427

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.607

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.631

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.595

AC:

869784

AN:

1461286

Hom.:

266970

Cov.:

AF XY:

0.595

AC XY:

432172

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.479

Gnomad4 FIN exome

AF:

0.511

Gnomad4 NFE exome

AF:

0.638

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.470

AC:

71409

AN:

151996

Hom.:

19470

Cov.:

AF XY:

0.464

AC XY:

34431

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.431

Gnomad4 ASJ

AF:

0.611

Gnomad4 EAS

AF:

0.346

Gnomad4 SAS

AF:

0.473

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.637

Gnomad4 OTH

AF:

0.514

Alfa

AF:

0.609

Hom.:

66134

Bravo

AF:

0.446

TwinsUK

AF:

0.638

AC:

2366

ALSPAC

AF:

0.645

AC:

2485

ESP6500AA

AF:

0.205

AC:

902

ESP6500EA

AF:

0.635

AC:

5463

ExAC

AF:

0.507

AC:

61503

Asia WGS

AF:

0.393

AC:

1369

AN:

3478

EpiCase

AF:

0.646

EpiControl

AF:

0.649

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Coronary artery spasm 3, susceptibility to

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.16

.;.;.;T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.32

T;T;T;.;T;T

MetaRNN

Benign

0.000017

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

L;L;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.63

N;N;N;.;N;N

REVEL

Benign

0.073

Sift

Benign

0.25

T;T;T;.;T;T

Sift4G

Benign

0.14

T;T;T;T;T;.

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.11

MPC

0.041

ClinPred

0.0093

GERP RS

-3.4

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over