Variant 12-125796-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_001170738.2(IQSEC3):c.787G>A(p.Gly263Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0109 in 1,522,940 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 5 hom., cov: 33)

Exomes 𝑓: 0.011 ( 120 hom. )

Consequence

IQSEC3
NM_001170738.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.73

Variant links:

Genes affected

IQSEC3 (HGNC:29193): (IQ motif and Sec7 domain ArfGEF 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of small GTPase mediated signal transduction. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IQSEC3 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 (MetaRNN=0.00622648).

BP6

Variant 12-125796-G-A is Benign according to our data. Variant chr12-125796-G-A is described in ClinVar as [Benign]. Clinvar id is 2642556.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC3	NM_001170738.2 linkuse as main transcript	c.787G>A	p.Gly263Ser	missense_variant	3/14	ENST00000538872.6	NP_001164209.1	Q9UPP2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC3	ENST00000538872.6 linkuse as main transcript	c.787G>A	p.Gly263Ser	missense_variant	3/14	5	NM_001170738.2	ENSP00000437554.1		Q9UPP2-1
IQSEC3	ENST00000382841.2 linkuse as main transcript	c.-6-12471G>A		intron_variant		2		ENSP00000372292.2		Q9UPP2-2

Frequencies

GnomAD3 genomes

AF:

0.00643

AC:

979

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00800

AC:

963

AN:

120334

Hom.:

AF XY:

0.00882

AC XY:

581

AN XY:

65880

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.00308

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00731

GnomAD4 exome

AF:

0.0114

AC:

15625

AN:

1370622

Hom.:

120

Cov.:

AF XY:

0.0113

AC XY:

7629

AN XY:

675724

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.00167

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.0000567

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.00306

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.00876

GnomAD4 genome

AF:

0.00643

AC:

980

AN:

152318

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

483

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00880

Hom.:

Bravo

AF:

0.00606

TwinsUK

AF:

0.0159

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.000801

AC:

ESP6500EA

AF:

0.00845

AC:

ExAC

AF:

0.00430

AC:

380

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

IQSEC3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.033

Eigen_PC

Benign

0.080

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

REVEL

Benign

0.12

Sift

Benign

0.46

Sift4G

Benign

0.74

Vest4

0.15

MVP

0.47

MPC

0.51

ClinPred

0.024

GERP RS

4.4

Varity_R

0.050

gMVP

0.17

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