Variant chr19-19633953-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016573.4(GMIP):c.2322C>T(p.Ser774Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.0031 in 1,583,914 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 25)

Exomes 𝑓: 0.0032 ( 10 hom. )

Consequence

GMIP
NM_016573.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.96

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 19-19633953-G-A is Benign according to our data. Variant chr19-19633953-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770552.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMIP	NM_016573.4 link	c.2322C>T	p.Ser774Ser	synonymous_variant	Exon 19 of 21	ENST00000203556.9	NP_057657.2	Q9P107-1A0A024R7N1B4DLZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMIP	ENST00000203556.9 link	c.2322C>T	p.Ser774Ser	synonymous_variant	Exon 19 of 21	1	NM_016573.4	ENSP00000203556.3		Q9P107-1
GMIP	ENST00000587238.5 link	c.2244C>T	p.Ser748Ser	synonymous_variant	Exon 18 of 20	1		ENSP00000467054.1		Q9P107-2

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

278

AN:

150266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000994

Gnomad ASJ

AF:

0.00982

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000481

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00215

AC:

507

AN:

236222

Hom.:

AF XY:

0.00235

AC XY:

303

AN XY:

129030

show subpopulations

Gnomad AFR exome

AF:

0.000599

Gnomad AMR exome

AF:

0.000539

Gnomad ASJ exome

AF:

0.00896

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000136

Gnomad FIN exome

AF:

0.000524

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.00208

GnomAD4 exome

AF:

0.00324

AC:

4639

AN:

1433530

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

2251

AN XY:

708528

show subpopulations

Gnomad4 AFR exome

AF:

0.000577

Gnomad4 AMR exome

AF:

0.000391

Gnomad4 ASJ exome

AF:

0.00955

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000825

Gnomad4 FIN exome

AF:

0.000597

Gnomad4 NFE exome

AF:

0.00382

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00185

AC:

278

AN:

150384

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

117

AN XY:

73404

show subpopulations

Gnomad4 AFR

AF:

0.000294

Gnomad4 AMR

AF:

0.000992

Gnomad4 ASJ

AF:

0.00982

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000481

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GMIP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.8

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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