Menu
GeneBe

chr9-136433147-G-GCGCCCACCCCTCCAGCCACGCCCACCCCTCCAGCCA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_019892.6(INPP5E):​c.1159+7_1159+8insTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 1 hom., cov: 28)
Exomes 𝑓: 0.0012 ( 5 hom. )
Failed GnomAD Quality Control

Consequence

INPP5E
NM_019892.6 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.695
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6
Variant 9-136433147-G-GCGCCCACCCCTCCAGCCACGCCCACCCCTCCAGCCA is Benign according to our data. Variant chr9-136433147-G-GCGCCCACCCCTCCAGCCACGCCCACCCCTCCAGCCA is described in ClinVar as [Likely_benign]. Clinvar id is 415747.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
INPP5ENM_019892.6 linkuse as main transcriptc.1159+7_1159+8insTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCG splice_region_variant, intron_variant ENST00000371712.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
INPP5EENST00000371712.4 linkuse as main transcriptc.1159+7_1159+8insTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCG splice_region_variant, intron_variant 1 NM_019892.6 P1Q9NRR6-1
INPP5EENST00000676019.1 linkuse as main transcriptc.1057+7_1057+8insTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCG splice_region_variant, intron_variant Q9NRR6-2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
121
AN:
148330
Hom.:
1
Cov.:
28
FAILED QC
Gnomad AFR
AF:
0.000103
Gnomad AMI
AF:
0.00442
Gnomad AMR
AF:
0.000134
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000964
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00163
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00117
AC:
1704
AN:
1451688
Hom.:
5
Cov.:
53
AF XY:
0.00112
AC XY:
808
AN XY:
722426
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.000247
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.0000215
Gnomad4 NFE exome
AF:
0.00146
Gnomad4 OTH exome
AF:
0.000997
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000815
AC:
121
AN:
148444
Hom.:
1
Cov.:
28
AF XY:
0.000607
AC XY:
44
AN XY:
72514
show subpopulations
Gnomad4 AFR
AF:
0.000103
Gnomad4 AMR
AF:
0.000134
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000964
Gnomad4 NFE
AF:
0.00163
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000242
Hom.:
959

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial aplasia of the vermis Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs71269007; hg19: chr9-139327599; API