Variant 19-19630042-G-A 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.2834C>T(p.Ser945Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,456,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000041 ( 0 hom. )

Consequence

GMIP
NM_016573.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

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=0.26385552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMIP	NM_016573.4 linkuse as main transcript	c.2834C>T	p.Ser945Leu	missense_variant	21/21	ENST00000203556.9	NP_057657.2	Q9P107-1A0A024R7N1B4DLZ1
GMIP	NM_001288999.2 linkuse as main transcript	c.2756C>T	p.Ser919Leu	missense_variant	20/20		NP_001275928.1	Q9P107-2B4DLZ1
GMIP	NM_001288998.2 linkuse as main transcript	c.2747C>T	p.Ser916Leu	missense_variant	20/20		NP_001275927.1	Q9P107B4DLZ1
GMIP	XM_005259927.3 linkuse as main transcript	c.2825C>T	p.Ser942Leu	missense_variant	21/21		XP_005259984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMIP	ENST00000203556.9 linkuse as main transcript	c.2834C>T	p.Ser945Leu	missense_variant	21/21	1	NM_016573.4	ENSP00000203556.3		Q9P107-1
GMIP	ENST00000587238.5 linkuse as main transcript	c.2756C>T	p.Ser919Leu	missense_variant	20/20	1		ENSP00000467054.1		Q9P107-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

236962

Hom.:

AF XY:

0.00000778

AC XY:

AN XY:

128616

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:

0.00000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456666

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724190

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000333

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

Nov 22, 2024

The c.2834C>T (p.S945L) alteration is located in exon 21 (coding exon 21) of the GMIP gene. This alteration results from a C to T substitution at nucleotide position 2834, causing the serine (S) at amino acid position 945 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

2.0

M;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.088

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.32

MutPred

0.20

Loss of phosphorylation at S945 (P = 0.0382);.;

MVP

0.61

MPC

0.73

ClinPred

0.84

GERP RS

4.0

Varity_R

0.15

gMVP

0.63

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