chr3-12901262-G-A

Position:

• chr3-12901262-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001134382.3(IQSEC1):​c.3066C>T​(p.Ala1022=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,540,788 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (10 hom.)
• Consequence: IQSEC1 NM_001134382.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33

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]

LOC105376956 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 3-12901262-G-A is Benign according to our data. Variant chr3-12901262-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1176149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.33 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQSEC1	NM_001134382.3	c.3066C>T	p.Ala1022=	synonymous_variant	14/14	ENST00000613206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQSEC1	ENST00000613206.2	c.3066C>T	p.Ala1022=	synonymous_variant	14/14	2	NM_001134382.3

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 207 AN: 144004 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00155

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00748

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00189

Gnomad OTH AF: 0.000995

GnomAD3 exomes AF: 0.00216 AC: 302 AN: 139818 Hom.: 6 AF XY: 0.00256 AC XY: 194 AN XY: 75922

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.000248

Gnomad ASJ exome AF: 0.000737

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00691

Gnomad FIN exome AF: 0.0000675

Gnomad NFE exome AF: 0.00245

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00225 AC: 3149 AN: 1396662 Hom.: 10 Cov.: 35 AF XY: 0.00239 AC XY: 1647 AN XY: 688858

Gnomad4 AFR exome AF: 0.000350

Gnomad4 AMR exome AF: 0.000505

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.00620

Gnomad4 FIN exome AF: 0.0000634

Gnomad4 NFE exome AF: 0.00229

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00144 AC: 207 AN: 144126 Hom.: 1 Cov.: 31 AF XY: 0.00150 AC XY: 106 AN XY: 70614

Gnomad4 AFR AF: 0.000322

Gnomad4 AMR AF: 0.00155

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00748

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00189

Gnomad4 OTH AF: 0.000984

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

IQSEC1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.9
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs571426372; hg19: chr3-12942761;