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GeneBe

3-12901211-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001134382.3(IQSEC1):c.3117G>A(p.Pro1039=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,545,674 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 175 hom., cov: 31)
Exomes 𝑓: 0.0029 ( 122 hom. )

Consequence

IQSEC1
NM_001134382.3 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.410
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-12901211-C-T is Benign according to our data. Variant chr3-12901211-C-T is described in ClinVar as [Benign]. Clinvar id is 783996.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.41 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IQSEC1NM_001134382.3 linkuse as main transcriptc.3117G>A p.Pro1039= synonymous_variant 14/14 ENST00000613206.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IQSEC1ENST00000613206.2 linkuse as main transcriptc.3117G>A p.Pro1039= synonymous_variant 14/142 NM_001134382.3 Q6DN90-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0261
AC:
3940
AN:
151216
Hom.:
174
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0887
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0136
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00188
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.000649
Gnomad OTH
AF:
0.0178
GnomAD3 exomes
AF:
0.00565
AC:
790
AN:
139766
Hom.:
20
AF XY:
0.00499
AC XY:
377
AN XY:
75556
show subpopulations
Gnomad AFR exome
AF:
0.0927
Gnomad AMR exome
AF:
0.00403
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00214
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000583
Gnomad OTH exome
AF:
0.00220
GnomAD4 exome
AF:
0.00289
AC:
4033
AN:
1394340
Hom.:
122
Cov.:
35
AF XY:
0.00255
AC XY:
1752
AN XY:
687540
show subpopulations
Gnomad4 AFR exome
AF:
0.0945
Gnomad4 AMR exome
AF:
0.00461
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.00193
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000320
Gnomad4 OTH exome
AF:
0.00625
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0260
AC:
3939
AN:
151334
Hom.:
175
Cov.:
31
AF XY:
0.0253
AC XY:
1867
AN XY:
73890
show subpopulations
Gnomad4 AFR
AF:
0.0884
Gnomad4 AMR
AF:
0.0136
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00167
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000649
Gnomad4 OTH
AF:
0.0176
Alfa
AF:
0.00369
Hom.:
22
Bravo
AF:
0.0302
Asia WGS
AF:
0.00433
AC:
16
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
9.4
Dann
Uncertain
0.98
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73141360; hg19: chr3-12942710; API