Variant 3-12901211-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001134382.3(IQSEC1):c.3117G>A(p.Pro1039Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,545,674 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 175 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 122 hom. )

Consequence

IQSEC1
NM_001134382.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.410

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 3-12901211-C-T is Benign according to our data. Variant chr3-12901211-C-T is described in ClinVar as [Benign]. Clinvar id is 783996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC1	NM_001134382.3 linkuse as main transcript	c.3117G>A	p.Pro1039Pro	synonymous_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 linkuse as main transcript	c.3117G>A	p.Pro1039Pro	synonymous_variant	14/14	2	NM_001134382.3	ENSP00000480301.1		Q6DN90-3

Frequencies

GnomAD3 genomes

AF:

0.0261

AC:

3940

AN:

151216

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0887

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00188

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000649

Gnomad OTH

AF:

0.0178

GnomAD3 exomes

AF:

0.00565

AC:

790

AN:

139766

Hom.:

AF XY:

0.00499

AC XY:

377

AN XY:

75556

show subpopulations

Gnomad AFR exome

AF:

0.0927

Gnomad AMR exome

AF:

0.00403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00214

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000583

Gnomad OTH exome

AF:

0.00220

GnomAD4 exome

AF:

0.00289

AC:

4033

AN:

1394340

Hom.:

122

Cov.:

AF XY:

0.00255

AC XY:

1752

AN XY:

687540

show subpopulations

Gnomad4 AFR exome

AF:

0.0945

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00193

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000320

Gnomad4 OTH exome

AF:

0.00625

GnomAD4 genome

AF:

0.0260

AC:

3939

AN:

151334

Hom.:

175

Cov.:

AF XY:

0.0253

AC XY:

1867

AN XY:

73890

show subpopulations

Gnomad4 AFR

AF:

0.0884

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000649

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.0302

Asia WGS

AF:

0.00433

AC:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.4

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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