3-12901258-TGGC-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_001134382.3(IQSEC1):c.3067_3069del(p.Ala1023del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,497,386 control chromosomes in the GnomAD database, including 315 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A1023A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.028 (181 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (134 hom.)
• Consequence: IQSEC1 NM_001134382.3 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33

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 -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001134382.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 3-12901258-TGGC-T is Benign according to our data. Variant chr3-12901258-TGGC-T is described in ClinVar as [Benign]. Clinvar id is 2855636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQSEC1	NM_001134382.3	c.3067_3069del	p.Ala1023del	inframe_deletion	14/14	ENST00000613206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQSEC1	ENST00000613206.2	c.3067_3069del	p.Ala1023del	inframe_deletion	14/14	2	NM_001134382.3

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4097 AN: 146828 Hom.: 180 Cov.: 31

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000676

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.000597

Gnomad OTH AF: 0.0202

GnomAD3 exomes AF: 0.00544 AC: 769 AN: 141388 Hom.: 22 AF XY: 0.00471 AC XY: 361 AN XY: 76664

Gnomad AFR exome AF: 0.0970

Gnomad AMR exome AF: 0.00409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000267

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000498

Gnomad OTH exome AF: 0.00242

GnomAD4 exome AF: 0.00299 AC: 4034 AN: 1350470 Hom.: 134 AF XY: 0.00254 AC XY: 1694 AN XY: 665914

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.00500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000315

Gnomad4 SAS exome AF: 0.000356

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000318

Gnomad4 OTH exome AF: 0.00681

GnomAD4 genome AF: 0.0279 AC: 4096 AN: 146916 Hom.: 181 Cov.: 31 AF XY: 0.0269 AC XY: 1924 AN XY: 71554

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000451

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000597

Gnomad4 OTH AF: 0.0200

Alfa AF: 0.0159 Hom.: 20

Bravo AF: 0.0316

Asia WGS AF: 0.00462 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs137962390; hg19: chr3-12942757;