rs11146014
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_019892.6(INPP5E):c.1549+23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 640,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 4)
Exomes 𝑓: 0.000012 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
INPP5E
NM_019892.6 intron
NM_019892.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.60
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.1549+23A>T | intron_variant | ENST00000371712.4 | |||
INPP5E | NM_001318502.2 | c.1546+23A>T | intron_variant | ||||
INPP5E | XM_017014926.2 | c.1549+23A>T | intron_variant | ||||
INPP5E | XM_047423603.1 | c.1546+23A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.1549+23A>T | intron_variant | 1 | NM_019892.6 | P1 | |||
INPP5E | ENST00000676019.1 | c.1447+23A>T | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 43592Hom.: 0 Cov.: 4 FAILED QC
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GnomAD4 exome AF: 0.0000125 AC: 8AN: 640440Hom.: 0 Cov.: 21 AF XY: 0.00000928 AC XY: 3AN XY: 323214
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 43592Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0AN XY: 20730
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at