19-38081727-GGCCACCGCCACCGCCACC-GGCCACCGCCACCGCCACCGCCACCGCCACC
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015073.3(SIPA1L3):c.181_192dupGCCACCGCCACC(p.Ala61_Thr64dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,072 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000069 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIPA1L3
NM_015073.3 conservative_inframe_insertion
NM_015073.3 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.25
Genes affected
SIPA1L3 (HGNC:23801): (signal induced proliferation associated 1 like 3) This gene belongs to the signal induced proliferation associated 1 family of genes, which encode GTPase-activating proteins specific for the GTP-binding protein Rap1. Rap1 has been implicated in regulation of cell adhesion, cell polarity, and organization of the cytoskeleton. Like other members of the family, the protein encoded by this gene contains RapGAP and PDZ domains. In addition, this protein contains a C-terminal leucine zipper domain. This gene is proposed to function in epithelial cell morphogenesis and establishment or maintenance of polarity. Consistently, expression of the protein in cell culture showed localization to cell-cell borders in apical regions, and downregulation of the gene in 3D Caco2 cell culture resulted in abnormal cell polarity and morphogenesis. Allelic variants of this gene have been associated with congenital cataracts in humans. [provided by RefSeq, Feb 2016]
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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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000689 AC: 100AN: 1450622Hom.: 0 Cov.: 30 AF XY: 0.0000707 AC XY: 51AN XY: 721320
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74290
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ClinVar
Not reported inComputational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at