9-136433147-G-GCGCCCACCCCTCCAGCCA
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_019892.6(INPP5E):c.1159+7_1159+8insTGGCTGGAGGGGTGGGCG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 147,718 control chromosomes in the GnomAD database, including 5,144 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.26 ( 5144 hom., cov: 28)
Exomes 𝑓: 0.29 ( 63852 hom. )
Failed GnomAD Quality Control
Consequence
INPP5E
NM_019892.6 splice_region, intron
NM_019892.6 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.695
Genes affected
INPP5E (HGNC:21474): (inositol polyphosphate-5-phosphatase E) The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. Studies of the mouse counterpart suggest that this protein may hydrolyze phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,5-bisphosphate on the cytoplasmic Golgi membrane and thereby regulate Golgi-vesicular trafficking. Mutations in this gene cause Joubert syndrome; a clinically and genetically heterogenous group of disorders characterized by midbrain-hindbrain malformation and various associated ciliopathies that include retinal dystrophy, nephronophthisis, liver fibrosis and polydactyly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 9-136433147-G-GCGCCCACCCCTCCAGCCA is Benign according to our data. Variant chr9-136433147-G-GCGCCCACCCCTCCAGCCA is described in ClinVar as [Likely_benign]. Clinvar id is 215526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.1159+7_1159+8insTGGCTGGAGGGGTGGGCG | splice_region_variant, intron_variant | Intron 4 of 9 | 1 | NM_019892.6 | ENSP00000360777.3 | |||
INPP5E | ENST00000676019.1 | c.1057+7_1057+8insTGGCTGGAGGGGTGGGCG | splice_region_variant, intron_variant | Intron 4 of 9 | ENSP00000501984.1 |
Frequencies
GnomAD3 genomes AF: 0.258 AC: 38034AN: 147600Hom.: 5142 Cov.: 28
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.289 AC: 417440AN: 1443622Hom.: 63852 Cov.: 53 AF XY: 0.285 AC XY: 204963AN XY: 718522
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.258 AC: 38065AN: 147718Hom.: 5144 Cov.: 28 AF XY: 0.252 AC XY: 18158AN XY: 72098
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
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PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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Oct 24, 2022
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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not provided Benign:2
Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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Familial aplasia of the vermis Benign:2
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Retinal dystrophy Benign:1
Jan 01, 2023
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at