rs953385

chr12-114256-G-Cchr12-114256-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001170738.2(IQSEC3):c.624-11377G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,092 control chromosomes in the GnomAD database, including 9,890 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 0.36 (9890 hom., cov: 33)
• Consequence: IQSEC3 NM_001170738.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQSEC3	NM_001170738.2	c.624-11377G>C		intron_variant		ENST00000538872.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQSEC3	ENST00000538872.6	c.624-11377G>C		intron_variant		5	NM_001170738.2	P1
IQSEC3	ENST00000382841.2	c.-7+15042G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54095 AN: 151974 Hom.: 9891 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.356 AC: 54086 AN: 152092 Hom.: 9890 Cov.: 33 AF XY: 0.357 AC XY: 26558 AN XY: 74344

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.333

Alfa AF: 0.264 Hom.: 752

Bravo AF: 0.346

Asia WGS AF: 0.329 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.4
Dann	Benign	0.68

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: rs953385; hg19: chr12-223422;