Variant chr3-12901078-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001134382.3(IQSEC1):c.3250G>A(p.Val1084Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,515,734 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 4 hom. )

Consequence

IQSEC1
NM_001134382.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.31

Variant links:

Genes affected

IQSEC1 (HGNC:29112): (IQ motif and Sec7 domain ArfGEF 1) Predicted to enable protein kinase binding activity. Predicted to be involved in several processes, including positive regulation of focal adhesion disassembly; positive regulation of keratinocyte migration; and regulation of postsynaptic neurotransmitter receptor internalization. Located in nucleolus. Implicated in intellectual developmental disorder with short stature and behavioral abnormalities. [provided by Alliance of Genome Resources, Apr 2022]

IQSEC1 links:

LOC105376956 (HGNC:):

LOC105376956 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002505958).

BP6

Variant 3-12901078-C-T is Benign according to our data. Variant chr3-12901078-C-T is described in ClinVar as [Benign]. Clinvar id is 783367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-12901078-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00615 (923/150160) while in subpopulation AFR AF= 0.0215 (884/41026). AF 95% confidence interval is 0.0204. There are 11 homozygotes in gnomad4. There are 411 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQSEC1	NM_001134382.3 linkuse as main transcript	c.3250G>A	p.Val1084Met	missense_variant	14/14	ENST00000613206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQSEC1	ENST00000613206.2 linkuse as main transcript	c.3250G>A	p.Val1084Met	missense_variant	14/14	2	NM_001134382.3		Q6DN90-3

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

922

AN:

150024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00152

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00143

AC:

201

AN:

140820

Hom.:

AF XY:

0.00108

AC XY:

AN XY:

75806

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.000863

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000445

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000554

Gnomad OTH exome

AF:

0.000722

GnomAD4 exome

AF:

0.000583

AC:

796

AN:

1365574

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

347

AN XY:

673584

show subpopulations

Gnomad4 AFR exome

AF:

0.0208

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.0000414

Gnomad4 EAS exome

AF:

0.0000291

Gnomad4 SAS exome

AF:

0.000114

Gnomad4 FIN exome

AF:

0.0000270

Gnomad4 NFE exome

AF:

0.0000385

Gnomad4 OTH exome

AF:

0.00107

GnomAD4 genome

AF:

0.00615

AC:

923

AN:

150160

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

411

AN XY:

73336

show subpopulations

Gnomad4 AFR

AF:

0.0215

Gnomad4 AMR

AF:

0.00152

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00717

ExAC

AF:

0.00188

AC:

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

Invitae

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.13

DANN

Benign

0.85

DEOGEN2

Benign

0.0071

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.68

PrimateAI

Uncertain

0.70

Sift4G

Benign

0.23

.;T

Vest4

0.18

MVP

0.10

ClinPred

0.0029

GERP RS

-7.4

gMVP

0.18

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