chr3-12901300-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001134382.3(IQSEC1):c.3028G>A(p.Gly1010Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,544,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1010D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

IQSEC1
NM_001134382.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.717

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder with short stature and behavioral abnormalities
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IQSEC1 links:

ENSG00000297478 (HGNC:):

ENSG00000297478 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024719775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134382.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQSEC1	NM_001134382.3	MANE Select	c.3028G>A	p.Gly1010Ser	missense	Exon 14 of 14	NP_001127854.1	Q6DN90-3
IQSEC1	NM_001376938.2		c.3352G>A	p.Gly1118Ser	missense	Exon 16 of 16	NP_001363867.1	A0A3B3IRZ4
IQSEC1	NM_001330619.3		c.*209G>A		3_prime_UTR	Exon 13 of 13	NP_001317548.1	A0A0C4DGT3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQSEC1	ENST00000613206.2	TSL:2 MANE Select	c.3028G>A	p.Gly1010Ser	missense	Exon 14 of 14	ENSP00000480301.1	Q6DN90-3
IQSEC1	ENST00000618604.4	TSL:1	c.*209G>A		3_prime_UTR	Exon 13 of 13	ENSP00000478001.1	A0A0C4DGT3
IQSEC1	ENST00000273221.8	TSL:1	c.2847+1473G>A		intron	N/A	ENSP00000273221.4	Q6DN90-1

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

150194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000593

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000851

AC:

AN:

140970

AF XY:

0.0000652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000258

AC:

AN:

1394454

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

687910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31520

American (AMR)

AF:

0.00

AC:

AN:

35644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25068

East Asian (EAS)

AF:

0.000703

AC:

AN:

35570

South Asian (SAS)

AF:

0.00

AC:

AN:

79166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5484

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1077792

Other (OTH)

AF:

0.000138

AC:

AN:

57820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000200

AC:

AN:

150306

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40664

American (AMR)

AF:

0.00

AC:

AN:

15064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000595

AC:

AN:

5044

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67686

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000353

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual developmental disorder with short stature and behavioral abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.1

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.69

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.96

PhyloP100

0.72

PrimateAI

Uncertain

0.71

Sift4G

Benign

0.77

Vest4

0.12

MVP

0.11

ClinPred

0.042

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.24

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over