chr12-110822-A-T

Position:

• chr12-110822-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170738.2(IQSEC3):​c.623+11608A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: IQSEC3 NM_001170738.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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]

ENSG00000256948 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC3	NM_001170738.2	c.623+11608A>T		intron_variant		ENST00000538872.6	NP_001164209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC3	ENST00000538872.6	c.623+11608A>T		intron_variant		5	NM_001170738.2	ENSP00000437554.1
IQSEC3	ENST00000382841.2	c.-7+11608A>T		intron_variant		2		ENSP00000372292.2
ENSG00000256948	ENST00000540226.1	n.232+797T>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.62

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: rs2011738; hg19: chr12-219988;