chr9-136428749-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_019892.6(INPP5E):c.*926T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,640 control chromosomes in the GnomAD database, including 1,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.11 ( 1175 hom., cov: 32)
Exomes 𝑓: 0.099 ( 4 hom. )
Consequence
INPP5E
NM_019892.6 3_prime_UTR
NM_019892.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.227
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 9-136428749-A-G is Benign according to our data. Variant chr9-136428749-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 365866.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.*926T>C | 3_prime_UTR_variant | 10/10 | ENST00000371712.4 | ||
INPP5E | NM_001318502.2 | c.*926T>C | 3_prime_UTR_variant | 10/10 | |||
INPP5E | XM_017014926.2 | c.*1005T>C | 3_prime_UTR_variant | 10/10 | |||
INPP5E | XM_047423603.1 | c.*1005T>C | 3_prime_UTR_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.*926T>C | 3_prime_UTR_variant | 10/10 | 1 | NM_019892.6 | P1 | ||
INPP5E | ENST00000676019.1 | c.*926T>C | 3_prime_UTR_variant | 10/10 |
Frequencies
GnomAD3 genomes ? AF: 0.113 AC: 17169AN: 152118Hom.: 1167 Cov.: 32
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GnomAD4 exome AF: 0.0990 AC: 40AN: 404Hom.: 4 Cov.: 0 AF XY: 0.107 AC XY: 24AN XY: 224
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Joubert syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
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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