Genetic Variant GMIP:p.Arg867His (chr19-19630276-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016573.4(GMIP):c.2600G>A(p.Arg867His) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,548,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

GMIP
NM_016573.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77

Publications

1 publications found

Variant links:

Genes affected

GMIP (HGNC:24852): (GEM interacting protein) This gene encodes a member of the ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. The encoded protein interacts with the Ras-related protein Gem through its N-terminal domain. Separately, it interacts with RhoA through a RhoGAP domain, and stimulates RhoA-dependent GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

GMIP links:

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ACMG classification

Classification was made for transcript

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=0.14339393).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016573.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GMIP	NM_016573.4	MANE Select	c.2600G>A	p.Arg867His	missense	Exon 21 of 21	NP_057657.2	Q9P107-1
GMIP	NM_001288999.2		c.2522G>A	p.Arg841His	missense	Exon 20 of 20	NP_001275928.1	Q9P107-2
GMIP	NM_001288998.2		c.2513G>A	p.Arg838His	missense	Exon 20 of 20	NP_001275927.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GMIP	ENST00000203556.9	TSL:1 MANE Select	c.2600G>A	p.Arg867His	missense	Exon 21 of 21	ENSP00000203556.3	Q9P107-1
GMIP	ENST00000587238.5	TSL:1	c.2522G>A	p.Arg841His	missense	Exon 20 of 20	ENSP00000467054.1	Q9P107-2
GMIP	ENST00000940889.1		c.2576G>A	p.Arg859His	missense	Exon 21 of 21	ENSP00000610948.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

192624

AF XY:

0.0000289

show subpopulations

Gnomad AFR exome

AF:

0.0000710

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000603

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000686

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1396590

Hom.:

Cov.:

AF XY:

0.0000218

AC XY:

AN XY:

687268

show subpopulations

African (AFR)

AF:

0.0000945

AC:

AN:

31742

American (AMR)

AF:

0.00

AC:

AN:

36780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21844

East Asian (EAS)

AF:

0.00

AC:

AN:

39016

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76438

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5448

European-Non Finnish (NFE)

AF:

0.0000334

AC:

AN:

1078400

Other (OTH)

AF:

0.0000174

AC:

AN:

57348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000394

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.0000210

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000505

AC:

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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.030

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

PhyloP100

5.8

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

REVEL

Benign

0.27

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.23

MVP

0.45

MPC

1.1

ClinPred

0.27

GERP RS

4.3

Varity_R

0.20

gMVP

0.46

Mutation Taster

=79/21

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