chr12-57478754-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032496.4(ARHGAP9):c.320C>T(p.Pro107Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 1,605,422 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

ARHGAP9
NM_032496.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease axonal type 2U
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
severe early-onset pulmonary alveolar proteinosis due to MARS deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
autosomal recessive spastic paraplegia type 70
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Charcot-Marie-Tooth disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
trichothiodystrophy 9, nonphotosensitive
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
spastic paraplegia 70, autosomal recessive
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.026905596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032496.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP9	NM_032496.4	MANE Select	c.320C>T	p.Pro107Leu	missense	Exon 3 of 18	NP_115885.2	Q9BRR9-2
ARHGAP9	NM_001319850.2		c.320C>T	p.Pro107Leu	missense	Exon 6 of 21	NP_001306779.2	Q9BRR9-1
ARHGAP9	NM_001080157.2		c.320C>T	p.Pro107Leu	missense	Exon 2 of 16	NP_001073626.1	Q9BRR9-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP9	ENST00000393791.8	TSL:1 MANE Select	c.320C>T	p.Pro107Leu	missense	Exon 3 of 18	ENSP00000377380.3	Q9BRR9-2
ARHGAP9	ENST00000393797.7	TSL:1	c.320C>T	p.Pro107Leu	missense	Exon 6 of 21	ENSP00000377386.3	Q9BRR9-1
ARHGAP9	ENST00000906774.1		c.320C>T	p.Pro107Leu	missense	Exon 2 of 17	ENSP00000576833.1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000369

AC:

AN:

246742

AF XY:

0.000329

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.000862

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000932

Gnomad NFE exome

AF:

0.000450

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000345

AC:

502

AN:

1453212

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

223

AN XY:

721642

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33132

American (AMR)

AF:

0.000983

AC:

AN:

43754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25826

East Asian (EAS)

AF:

0.00

AC:

AN:

39510

South Asian (SAS)

AF:

0.000198

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000373

AC:

413

AN:

1106004

Other (OTH)

AF:

0.000400

AC:

AN:

59932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000309

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41518

American (AMR)

AF:

0.00151

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000378

Hom.:

Bravo

AF:

0.000400

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.021

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.85

M_CAP

Benign

0.011

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

1.5

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

REVEL

Benign

0.056

Sift

Uncertain

0.011

Sift4G

Benign

0.099

Polyphen

0.52

Vest4

0.40

MVP

0.73

MPC

0.051

ClinPred

0.023

GERP RS

3.5

PromoterAI

-0.0040

Neutral

(source)

gMVP

0.34

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over