chr3-12901349-T-G

Position:

• chr3-12901349-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001134382.3(IQSEC1):​c.2979A>C​(p.Pro993=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IQSEC1 NM_001134382.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-12901349-T-G is Benign according to our data. Variant chr3-12901349-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQSEC1	NM_001134382.3	c.2979A>C	p.Pro993=	synonymous_variant	14/14	ENST00000613206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQSEC1	ENST00000613206.2	c.2979A>C	p.Pro993=	synonymous_variant	14/14	2	NM_001134382.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 55 AN: 118240 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000331

Gnomad ASJ AF: 0.000346

Gnomad EAS AF: 0.00167

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000425

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000380

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000432 AC: 2 AN: 4634 Hom.: 0 AF XY: 0.000421 AC XY: 1 AN XY: 2376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00151

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00115 AC: 1035 AN: 901498 Hom.: 0 Cov.: 28 AF XY: 0.00108 AC XY: 487 AN XY: 451214

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.000773

Gnomad4 ASJ exome AF: 0.00263

Gnomad4 EAS exome AF: 0.00704

Gnomad4 SAS exome AF: 0.000256

Gnomad4 FIN exome AF: 0.00314

Gnomad4 NFE exome AF: 0.000995

Gnomad4 OTH exome AF: 0.00196

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000448 AC: 53 AN: 118296 Hom.: 0 Cov.: 31 AF XY: 0.000399 AC XY: 23 AN XY: 57638

Gnomad4 AFR AF: 0.000380

Gnomad4 AMR AF: 0.000330

Gnomad4 ASJ AF: 0.000346

Gnomad4 EAS AF: 0.00139

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000425

Gnomad4 NFE AF: 0.000380

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0169 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

IQSEC1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.054

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: rs866819128; hg19: chr3-12942848; COSMIC: COSV56223494;