3-12898047-G-A

Position:

• chr3-12898047-G-A

Variant summary

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

The NM_001134382.3(IQSEC1):​c.*2936C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,264 control chromosomes in the GnomAD database, including 50,208 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 0.80 (50203 hom., cov: 34)
  • Exomes 𝑓: 0.72 (5 hom.)
• Consequence: IQSEC1 NM_001134382.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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]

LOC105376956 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQSEC1	NM_001134382.3	c.*2936C>T		3_prime_UTR_variant	14/14	ENST00000613206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQSEC1	ENST00000613206.2	c.*2936C>T		3_prime_UTR_variant	14/14	2	NM_001134382.3
IQSEC1	ENST00000273221.8	c.*1343C>T		3_prime_UTR_variant	14/14	1		P3
IQSEC1	ENST00000646269.1	c.*1343C>T		3_prime_UTR_variant	14/14

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122393 AN: 152130 Hom.: 50152 Cov.: 34

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.777

GnomAD4 exome AF: 0.722 AC: 13 AN: 18 Hom.: 5 Cov.: 0 AF XY: 0.857 AC XY: 12 AN XY: 14

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.805 AC: 122494 AN: 152246 Hom.: 50203 Cov.: 34 AF XY: 0.797 AC XY: 59349 AN XY: 74434

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.776

Alfa AF: 0.796 Hom.: 27932

Bravo AF: 0.805

Asia WGS AF: 0.574 AC: 2000 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	0.48
DANN	Benign	0.43

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: rs9211; hg19: chr3-12939546;