ClinVar Miner

Submissions for variant NM_001080453.3(INTS1):c.3679G>C (p.Glu1227Gln)

gnomAD frequency: 0.00010  dbSNP: rs758158889
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001281493 SCV001468802 uncertain significance Dandy-Walker syndrome; Global developmental delay 2019-09-13 criteria provided, single submitter clinical testing The inherited c.3679G>C (p.Glu1227Gln) variant identified in the INTS1 gene substitutes a completely conserved Glutamic Acid for Glutamine at amino acidat aminoacid 1227/2191 (coding exon 47/48). This variant is found in gnomAD (64 heterozygotes, 0 homozygotes; allele frequency: 2.29e-4) and ExAC (20 heterozygotes, 0 homozygotes; allele frequency: 1.69e-4). In silico algorithms predict this variant to be Neutral (Provean; score:-0.54) and Tolerated (SIFT; score:0.134) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. Given the lack of compelling evidence supporting its pathogenicity, the c.3679G>C (p.Glu1227Gln) variant identified in the INTS1 gene is reported here as a Variant of Uncertain Significiance.
Ambry Genetics RCV003284136 SCV003980521 likely benign Inborn genetic diseases 2023-03-31 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV003329396 SCV004036297 uncertain significance not provided 2023-03-22 criteria provided, single submitter clinical testing In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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