Variant rs367825362 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016573.4(GMIP):c.2551G>C(p.Gly851Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,386,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

GMIP
NM_016573.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.653

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041868806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4 link	c.2551G>C	p.Gly851Arg	missense_variant	Exon 21 of 21	ENST00000203556.9	NP_057657.2	Q9P107-1A0A024R7N1B4DLZ1
GMIP	NM_001288999.2 link	c.2473G>C	p.Gly825Arg	missense_variant	Exon 20 of 20		NP_001275928.1	Q9P107-2B4DLZ1
GMIP	NM_001288998.2 link	c.2464G>C	p.Gly822Arg	missense_variant	Exon 20 of 20		NP_001275927.1	Q9P107B4DLZ1
GMIP	XM_005259927.3 link	c.2542G>C	p.Gly848Arg	missense_variant	Exon 21 of 21		XP_005259984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMIP	ENST00000203556.9 link	c.2551G>C	p.Gly851Arg	missense_variant	Exon 21 of 21	1	NM_016573.4	ENSP00000203556.3		Q9P107-1
GMIP	ENST00000587238.5 link	c.2473G>C	p.Gly825Arg	missense_variant	Exon 20 of 20	1		ENSP00000467054.1		Q9P107-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000527

AC:

AN:

189794

Hom.:

AF XY:

0.00000995

AC XY:

AN XY:

100472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1386920

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

681414

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000335

Gnomad4 OTH exome

AF:

0.0000350

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0080

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.48

N;.

REVEL

Benign

0.040

Sift

Benign

0.43

T;.

Sift4G

Benign

0.12

T;T

Polyphen

0.78

P;.

Vest4

0.073

MutPred

0.11

Gain of solvent accessibility (P = 0.0456);.;

MVP

0.37

MPC

0.33

ClinPred

0.11

GERP RS

3.1

Varity_R

0.035

gMVP

0.22

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over