Variant 19-19629977-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.2899G>A(p.Glu967Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,608,858 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

GMIP
NM_016573.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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 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=0.10396734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4 link	c.2899G>A	p.Glu967Lys	missense_variant	Exon 21 of 21	ENST00000203556.9	NP_057657.2	Q9P107-1A0A024R7N1B4DLZ1
GMIP	NM_001288999.2 link	c.2821G>A	p.Glu941Lys	missense_variant	Exon 20 of 20		NP_001275928.1	Q9P107-2B4DLZ1
GMIP	NM_001288998.2 link	c.2812G>A	p.Glu938Lys	missense_variant	Exon 20 of 20		NP_001275927.1	Q9P107B4DLZ1
GMIP	XM_005259927.3 link	c.2890G>A	p.Glu964Lys	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.2899G>A	p.Glu967Lys	missense_variant	Exon 21 of 21	1	NM_016573.4	ENSP00000203556.3		Q9P107-1
GMIP	ENST00000587238.5 link	c.2821G>A	p.Glu941Lys	missense_variant	Exon 20 of 20	1		ENSP00000467054.1		Q9P107-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152158

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000546

AC:

AN:

238138

Hom.:

AF XY:

0.0000928

AC XY:

AN XY:

129296

show subpopulations

Gnomad AFR exome

AF:

0.000202

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000278

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1456582

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

724098

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000333

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2899G>A (p.E967K) 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 2899, causing the glutamic acid (E) at amino acid position 967 to be replaced by a lysine (K). 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

0.074

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.080

N;.

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;.

Vest4

0.23

MVP

0.50

MPC

0.57

ClinPred

0.16

GERP RS

3.6

Varity_R

0.080

gMVP

0.47

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