Genetic Variant NM_024605.4:c.706C>G (chr4-147875024-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_024605.4(ARHGAP10):c.706C>G(p.Arg236Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,580,428 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R236W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ARHGAP10
NM_024605.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Publications

1 publications found

Variant links:

Genes affected

ARHGAP10 (HGNC:26099): (Rho GTPase activating protein 10) Predicted to enable GTPase activator activity. Predicted to be involved in cytoskeleton organization and negative regulation of apoptotic process. Predicted to be located in perinuclear region of cytoplasm and plasma membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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_024605.4. 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
	ARHGAP10	NM_024605.4	MANE Select	c.706C>G	p.Arg236Gly	missense	Exon 8 of 23	NP_078881.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP10	ENST00000336498.8	TSL:1 MANE Select	c.706C>G	p.Arg236Gly	missense	Exon 8 of 23	ENSP00000336923.3	A1A4S6
ARHGAP10	ENST00000506054.5	TSL:1	n.5838C>G		non_coding_transcript_exon	Exon 2 of 17
ARHGAP10	ENST00000959974.1		c.793C>G	p.Arg265Gly	missense	Exon 9 of 24	ENSP00000630033.1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000152

AC:

AN:

223524

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00176

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

166

AN:

1428346

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

710222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35056

Ashkenazi Jewish (ASJ)

AF:

0.00252

AC:

AN:

24588

East Asian (EAS)

AF:

0.00

AC:

AN:

38942

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52854

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.0000799

AC:

AN:

1101658

Other (OTH)

AF:

0.000238

AC:

AN:

58872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000138

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41394

American (AMR)

AF:

0.000131

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68022

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000293

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.0055

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

1.6

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.27

Sift

Uncertain

0.014

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.89

MVP

0.43

MPC

0.66

ClinPred

0.82

GERP RS

2.8

Varity_R

0.73

gMVP

0.79

Mutation Taster

=35/65

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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