3-151436990-A-ACAAT
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178822.5(IGSF10):c.7567_7570dupATTG(p.Val2524fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
IGSF10
NM_178822.5 frameshift
NM_178822.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0990
Genes affected
IGSF10 (HGNC:26384): (immunoglobulin superfamily member 10) Predicted to be involved in regulation of neuron migration. Predicted to act upstream of or within ossification. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IGSF10 | NM_178822.5 | c.7567_7570dupATTG | p.Val2524fs | frameshift_variant | 8/8 | ENST00000282466.4 | NP_849144.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251372Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135852
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461884Hom.: 0 Cov.: 56 AF XY: 0.0000426 AC XY: 31AN XY: 727244
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74374
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 24, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1441895). This variant has not been reported in the literature in individuals affected with IGSF10-related conditions. This variant is present in population databases (rs746719746, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Val2524Aspfs*44) in the IGSF10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 100 amino acid(s) of the IGSF10 protein. - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at