chrX-53234223-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_ModerateBP4
The NM_001111125.3(IQSEC2):āc.4463T>Cā(p.Val1488Ala) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ).
Frequency
Genomes: not found (cov: 17)
Exomes š: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
IQSEC2
NM_001111125.3 missense
NM_001111125.3 missense
Scores
5
2
8
Clinical Significance
Conservation
PhyloP100: 7.11
Genes affected
IQSEC2 (HGNC:29059): (IQ motif and Sec7 domain ArfGEF 2) This gene encodes a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. The encoded protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates including ARF1 and ARF6. Mutations in this gene have been implicated in nonsyndromic X-linked cognitive disability. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP5
Variant X-53234223-A-G is Pathogenic according to our data. Variant chrX-53234223-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 449855.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.3111923). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQSEC2 | NM_001111125.3 | c.4463T>C | p.Val1488Ala | missense_variant | 15/15 | ENST00000642864.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQSEC2 | ENST00000642864.1 | c.4463T>C | p.Val1488Ala | missense_variant | 15/15 | NM_001111125.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 17
GnomAD3 genomes
Cov.:
17
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 923177Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0AN XY: 262443
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
923177
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Cov.:
17
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0
AN XY:
262443
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 17
GnomAD4 genome
Cov.:
17
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2019 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;.
Vest4
MutPred
Gain of glycosylation at S1485 (P = 0.1738);Gain of glycosylation at S1485 (P = 0.1738);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at