Genetic Variant GMIP:p.Gly805Ser (chr19-19633862-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_016573.4(GMIP):c.2413G>A(p.Gly805Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000994 in 1,387,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000087 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

GMIP
NM_016573.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.559

Publications

0 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:

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=0.019084781).

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.2413G>A	p.Gly805Ser	missense	Exon 19 of 21	NP_057657.2	Q9P107-1
GMIP	NM_001288999.2		c.2335G>A	p.Gly779Ser	missense	Exon 18 of 20	NP_001275928.1	Q9P107-2
GMIP	NM_001288998.2		c.2326G>A	p.Gly776Ser	missense	Exon 18 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.2413G>A	p.Gly805Ser	missense	Exon 19 of 21	ENSP00000203556.3	Q9P107-1
GMIP	ENST00000587238.5	TSL:1	c.2335G>A	p.Gly779Ser	missense	Exon 18 of 20	ENSP00000467054.1	Q9P107-2
GMIP	ENST00000940889.1		c.2389G>A	p.Gly797Ser	missense	Exon 19 of 21	ENSP00000610948.1

Frequencies

GnomAD3 genomes

AF:

0.0000869

AC:

AN:

126638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000597

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:

0.000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000147

AC:

AN:

149616

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.0000792

Gnomad AMR exome

AF:

0.000935

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

127

AN:

1261120

Hom.:

Cov.:

AF XY:

0.0000831

AC XY:

AN XY:

614046

show subpopulations

African (AFR)

AF:

0.0000365

AC:

AN:

27380

American (AMR)

AF:

0.000633

AC:

AN:

23714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16106

East Asian (EAS)

AF:

0.00

AC:

AN:

31530

South Asian (SAS)

AF:

0.00

AC:

AN:

67768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3572

European-Non Finnish (NFE)

AF:

0.000107

AC:

107

AN:

1000444

Other (OTH)

AF:

0.0000806

AC:

AN:

49632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.0000869

AC:

AN:

126638

Hom.:

Cov.:

AF XY:

0.0000663

AC XY:

AN XY:

60366

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33528

American (AMR)

AF:

0.00

AC:

AN:

11930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3166

East Asian (EAS)

AF:

0.00

AC:

AN:

4084

South Asian (SAS)

AF:

0.00

AC:

AN:

3724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000149

AC:

AN:

60430

Other (OTH)

AF:

0.00

AC:

AN:

1728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.0000822

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000136

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

Benign

0.072

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.32

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.62

M_CAP

Benign

0.0034

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

-0.56

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.19

REVEL

Benign

0.029

Sift

Benign

0.84

Sift4G

Benign

0.44

Polyphen

0.016

Vest4

0.075

MVP

0.17

MPC

0.27

ClinPred

0.0039

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.013

gMVP

0.10

Mutation Taster

=90/10

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