Variant 19-19630051-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016573.4(GMIP):c.2825G>A(p.Arg942Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,457,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GMIP
NM_016573.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16709203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GMIP	NM_016573.4 linkuse as main transcript	c.2825G>A	p.Arg942Gln	missense_variant	21/21	ENST00000203556.9
GMIP	NM_001288999.2 linkuse as main transcript	c.2747G>A	p.Arg916Gln	missense_variant	20/20
GMIP	NM_001288998.2 linkuse as main transcript	c.2738G>A	p.Arg913Gln	missense_variant	20/20
GMIP	XM_005259927.3 linkuse as main transcript	c.2816G>A	p.Arg939Gln	missense_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMIP	ENST00000203556.9 linkuse as main transcript	c.2825G>A	p.Arg942Gln	missense_variant	21/21	1	NM_016573.4	P1	Q9P107-1
GMIP	ENST00000587238.5 linkuse as main transcript	c.2747G>A	p.Arg916Gln	missense_variant	20/20	1			Q9P107-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457000

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724360

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:

0.00000631

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.2825G>A (p.R942Q) alteration is located in exon 21 (coding exon 21) of the GMIP gene. This alteration results from a G to A substitution at nucleotide position 2825, causing the arginine (R) at amino acid position 942 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.82

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.84

N;.

REVEL

Benign

0.054

Sift

Benign

0.046

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.65

P;.

Vest4

0.29

MutPred

0.23

Loss of phosphorylation at S945 (P = 0.0616);.;

MVP

0.44

MPC

0.42

ClinPred

0.80

GERP RS

5.1

Varity_R

0.21

gMVP

0.27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over