12-110822-A-G

Variant names:

• chr12-110822-A-G
• rs2011738
• NM_001170738.2:c.623+11608A>G

Variant summary

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

The NM_001170738.2(IQSEC3):​c.623+11608A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,890 control chromosomes in the GnomAD database, including 13,927 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 0.41 (13927 hom., cov: 31)
• Consequence: IQSEC3 NM_001170738.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 5 publications found

Genes affected

IQSEC3 (HGNC:29193): (IQ motif and Sec7 domain ArfGEF 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of small GTPase mediated signal transduction. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IQSEC3-AS2 (HGNC:56741): (IQSEC3 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC3	NM_001170738.2	c.623+11608A>G		intron_variant	Intron 2 of 13	ENST00000538872.6	NP_001164209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQSEC3	ENST00000538872.6	c.623+11608A>G		intron_variant	Intron 2 of 13	5	NM_001170738.2	ENSP00000437554.1
IQSEC3	ENST00000382841.2	c.-7+11608A>G		intron_variant	Intron 2 of 12	2		ENSP00000372292.2
IQSEC3-AS2	ENST00000540226.2	n.346+797T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62845 AN: 151774 Hom.: 13918 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.414 AC: 62896 AN: 151890 Hom.: 13927 Cov.: 31 AF XY: 0.419 AC XY: 31122 AN XY: 74244

African (AFR) AF: 0.400 AC: 16540 AN: 41400

American (AMR) AF: 0.505 AC: 7721 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1895 AN: 3466

East Asian (EAS) AF: 0.834 AC: 4303 AN: 5162

South Asian (SAS) AF: 0.605 AC: 2911 AN: 4810

European-Finnish (FIN) AF: 0.309 AC: 3264 AN: 10550

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24808 AN: 67916

Other (OTH) AF: 0.431 AC: 907 AN: 2106

Alfa AF: 0.396 Hom.: 37897

Bravo AF: 0.430

Asia WGS AF: 0.669 AC: 2326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.63
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2011738; hg19: chr12-219988;