chr9-136429670-A-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_019892.6(INPP5E):c.*5T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
INPP5E
NM_019892.6 3_prime_UTR
NM_019892.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.62
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 -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 9-136429670-A-C is Benign according to our data. Variant chr9-136429670-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3042809.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.*5T>G | 3_prime_UTR_variant | 10/10 | ENST00000371712.4 | ||
INPP5E | NM_001318502.2 | c.*5T>G | 3_prime_UTR_variant | 10/10 | |||
INPP5E | XM_017014926.2 | c.*84T>G | 3_prime_UTR_variant | 10/10 | |||
INPP5E | XM_047423603.1 | c.*84T>G | 3_prime_UTR_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.*5T>G | 3_prime_UTR_variant | 10/10 | 1 | NM_019892.6 | P1 | ||
INPP5E | ENST00000676019.1 | c.*5T>G | 3_prime_UTR_variant | 10/10 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152266Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251402Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135894
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461660Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727148
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152384Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74516
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
INPP5E-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 14, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at