3-13046812-A-G

Variant names:

• chr3-13046812-A-G
• rs360902
• NM_001134382.3:c.23+26180T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134382.3(IQSEC1):​c.23+26180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,650 control chromosomes in the GnomAD database, including 11,324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11324 hom., cov: 32)
• Consequence: IQSEC1 NM_001134382.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 3 publications found

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQSEC1	NM_001134382.3	MANE Select	c.23+26180T>C		intron	N/A	NP_001127854.1
	IQSEC1	NM_001376938.2		c.347+666T>C		intron	N/A	NP_001363867.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQSEC1	ENST00000613206.2	TSL:2 MANE Select	c.23+26180T>C		intron	N/A	ENSP00000480301.1
	IQSEC1	ENST00000648114.1		c.347+666T>C		intron	N/A	ENSP00000497029.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56051 AN: 151530 Hom.: 11306 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56089 AN: 151650 Hom.: 11324 Cov.: 32 AF XY: 0.375 AC XY: 27794 AN XY: 74068

African (AFR) AF: 0.227 AC: 9396 AN: 41380

American (AMR) AF: 0.524 AC: 7975 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3470

East Asian (EAS) AF: 0.644 AC: 3299 AN: 5126

South Asian (SAS) AF: 0.412 AC: 1987 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3856 AN: 10492

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27202 AN: 67840

Other (OTH) AF: 0.375 AC: 790 AN: 2108

Alfa AF: 0.399 Hom.: 2220

Bravo AF: 0.380

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.79
DANN	Benign	0.85
PhyloP100		-0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs360902; hg19: chr3-13088312;