12-120181-A-G

Variant names:

• chr12-120181-A-G
• rs904664
• NM_001170738.2:c.624-5452A>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.624-5452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 152,264 control chromosomes in the GnomAD database, including 69,373 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 0.95 (69373 hom., cov: 33)
• Consequence: IQSEC3 NM_001170738.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 1 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]

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 (NFE) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC3	NM_001170738.2	c.624-5452A>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.624-5452A>G		intron_variant	Intron 2 of 13	5	NM_001170738.2	ENSP00000437554.1
IQSEC3	ENST00000382841.2	c.-6-18086A>G		intron_variant	Intron 2 of 12	2		ENSP00000372292.2

Frequencies

GnomAD3 genomes AF: 0.953 AC: 145007 AN: 152146 Hom.: 69331 Cov.: 33

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.953 AC: 145104 AN: 152264 Hom.: 69373 Cov.: 33 AF XY: 0.954 AC XY: 71004 AN XY: 74448

African (AFR) AF: 0.861 AC: 35755 AN: 41512

American (AMR) AF: 0.969 AC: 14821 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3432 AN: 3468

East Asian (EAS) AF: 0.967 AC: 5009 AN: 5178

South Asian (SAS) AF: 0.971 AC: 4689 AN: 4828

European-Finnish (FIN) AF: 0.997 AC: 10583 AN: 10620

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67600 AN: 68042

Other (OTH) AF: 0.957 AC: 2024 AN: 2114

Alfa AF: 0.953 Hom.: 12119

Bravo AF: 0.948

Asia WGS AF: 0.974 AC: 3389 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	9.4
DANN	Benign	0.73
PhyloP100		0.072
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: rs904664; hg19: chr12-229347;