Variant 3-12901261-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001134382.3(IQSEC1):c.3067G>C(p.Ala1023Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 1,530,954 control chromosomes in the GnomAD database, including 63 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 0.013 ( 29 hom., cov: 31)

Exomes 𝑓: 0.0057 ( 34 hom. )

Consequence

IQSEC1
NM_001134382.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031626523).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (1914/143076) while in subpopulation AFR AF= 0.0417 (1417/33990). AF 95% confidence interval is 0.0399. There are 29 homozygotes in gnomad4. There are 876 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC1	NM_001134382.3 link	c.3067G>C	p.Ala1023Pro	missense_variant	14/14	ENST00000613206.2	NP_001127854.1	Q6DN90-3B4DGC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC1	ENST00000613206.2 link	c.3067G>C	p.Ala1023Pro	missense_variant	14/14	2	NM_001134382.3	ENSP00000480301.1		Q6DN90-3

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

1897

AN:

142960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00761

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000424

Gnomad FIN

AF:

0.00222

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.00494

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00452

AC:

637

AN:

141068

Hom.:

AF XY:

0.00400

AC XY:

306

AN XY:

76506

show subpopulations

Gnomad AFR exome

AF:

0.0357

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.000491

Gnomad EAS exome

AF:

0.000280

Gnomad SAS exome

AF:

0.000312

Gnomad FIN exome

AF:

0.00156

Gnomad NFE exome

AF:

0.00474

Gnomad OTH exome

AF:

0.00461

GnomAD4 exome

AF:

0.00565

AC:

7843

AN:

1387878

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

3647

AN XY:

685024

show subpopulations

Gnomad4 AFR exome

AF:

0.0414

Gnomad4 AMR exome

AF:

0.00482

Gnomad4 ASJ exome

AF:

0.000518

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.000253

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00556

Gnomad4 OTH exome

AF:

0.00823

GnomAD4 genome

AF:

0.0134

AC:

1914

AN:

143076

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

876

AN XY:

69992

show subpopulations

Gnomad4 AFR

AF:

0.0417

Gnomad4 AMR

AF:

0.00759

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000424

Gnomad4 FIN

AF:

0.00222

Gnomad4 NFE

AF:

0.00494

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.000366

Hom.:

Bravo

AF:

0.0144

ExAC

AF:

0.00216

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	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.7

DANN

Benign

0.46

DEOGEN2

Benign

0.0027

.;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.59

Sift4G

Benign

0.34

.;T

Vest4

0.16

MVP

0.082

ClinPred

0.0022

GERP RS

3.1

gMVP

0.44

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