chr3-12898330-T-C

Variant names:

• chr3-12898330-T-C
• rs11128623
• NM_001134382.3:c.*2653A>G

Variant summary

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

The NM_001134382.3(IQSEC1):​c.*2653A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,320 control chromosomes in the GnomAD database, including 1,028 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 0.081 (1028 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IQSEC1 NM_001134382.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

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 = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC1	NM_001134382.3	c.*2653A>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000613206.2	NP_001127854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQSEC1	ENST00000613206	c.*2653A>G		3_prime_UTR_variant	Exon 14 of 14	2	NM_001134382.3	ENSP00000480301.1
IQSEC1	ENST00000273221	c.*1060A>G		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000273221.4
IQSEC1	ENST00000646269	c.*1060A>G		3_prime_UTR_variant	Exon 14 of 14			ENSP00000496366.1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12311 AN: 152202 Hom.: 1015 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0286

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0611

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0811 AC: 12352 AN: 152320 Hom.: 1028 Cov.: 33 AF XY: 0.0803 AC XY: 5983 AN XY: 74500

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.0280

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0376 Hom.: 260

Bravo AF: 0.0888

Asia WGS AF: 0.0410 AC: 143 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	0.80
DANN	Benign	0.72

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: rs11128623; hg19: chr3-12939829;