3-12901289-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001134382.3(IQSEC1):c.3039G>A(p.Leu1013=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,546,348 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
IQSEC1
NM_001134382.3 synonymous
NM_001134382.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.518
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 3-12901289-C-T is Benign according to our data. Variant chr3-12901289-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 734117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.518 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQSEC1 | NM_001134382.3 | c.3039G>A | p.Leu1013= | synonymous_variant | 14/14 | ENST00000613206.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQSEC1 | ENST00000613206.2 | c.3039G>A | p.Leu1013= | synonymous_variant | 14/14 | 2 | NM_001134382.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00103 AC: 155AN: 150048Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000248 AC: 35AN: 141124Hom.: 0 AF XY: 0.000183 AC XY: 14AN XY: 76670
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GnomAD4 exome AF: 0.000112 AC: 156AN: 1396194Hom.: 0 Cov.: 35 AF XY: 0.000102 AC XY: 70AN XY: 688612
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GnomAD4 genome ? AF: 0.00103 AC: 155AN: 150154Hom.: 1 Cov.: 31 AF XY: 0.00130 AC XY: 95AN XY: 73256
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2018 | - - |
IQSEC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 22, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at