Variant 12-66923-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001170738.2(IQSEC3):c.41A>G(p.Tyr14Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00233 in 1,435,110 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

IQSEC3
NM_001170738.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.12

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054054618).

BP6

Variant 12-66923-A-G is Benign according to our data. Variant chr12-66923-A-G is described in ClinVar as [Benign]. Clinvar id is 778075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC3	NM_001170738.2 linkuse as main transcript	c.41A>G	p.Tyr14Cys	missense_variant	1/14	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.41A>G	p.Tyr14Cys	missense_variant	1/14	5	NM_001170738.2	ENSP00000437554.1		Q9UPP2-1

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

356

AN:

149542

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000880

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00126

Gnomad ASJ

AF:

0.00263

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00128

Gnomad FIN

AF:

0.000389

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00417

Gnomad OTH

AF:

0.00146

GnomAD4 exome

AF:

0.00233

AC:

2990

AN:

1285458

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1636

AN XY:

631852

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.00265

Gnomad4 ASJ exome

AF:

0.00479

Gnomad4 EAS exome

AF:

0.0000915

Gnomad4 SAS exome

AF:

0.00421

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00238

AC:

356

AN:

149652

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

141

AN XY:

73116

show subpopulations

Gnomad4 AFR

AF:

0.000878

Gnomad4 AMR

AF:

0.00126

Gnomad4 ASJ

AF:

0.00263

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00128

Gnomad4 FIN

AF:

0.000389

Gnomad4 NFE

AF:

0.00417

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00508

Hom.:

ExAC

AF:

0.000493

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.12

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.30

Sift

Uncertain

0.016

Sift4G

Pathogenic

0.0010

Vest4

0.72

MVP

0.60

MPC

3.5

ClinPred

0.053

GERP RS

3.7

Varity_R

0.30

gMVP

0.77

Splicing

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