Variant chr9-136431801-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019892.6(INPP5E):c.1549+23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 1901 hom., cov: 4)

Exomes 𝑓: 0.19 ( 14310 hom. )

Failed GnomAD Quality Control

Consequence

INPP5E
NM_019892.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.60

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]

INPP5E links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 9-136431801-T-C is Benign according to our data. Variant chr9-136431801-T-C is described in ClinVar as [Benign]. Clinvar id is 261197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
INPP5E	NM_019892.6 linkuse as main transcript	c.1549+23A>G	intron_variant	ENST00000371712.4
INPP5E	NM_001318502.2 linkuse as main transcript	c.1546+23A>G	intron_variant
INPP5E	XM_017014926.2 linkuse as main transcript	c.1549+23A>G	intron_variant
INPP5E	XM_047423603.1 linkuse as main transcript	c.1546+23A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP5E	ENST00000371712.4 linkuse as main transcript	c.1549+23A>G		intron_variant		1	NM_019892.6	P1	Q9NRR6-1
INPP5E	ENST00000676019.1 linkuse as main transcript	c.1447+23A>G		intron_variant					Q9NRR6-2

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

12719

AN:

43248

Hom.:

1904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.391

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.256

GnomAD3 exomes

AF:

0.163

AC:

17607

AN:

107742

Hom.:

2967

AF XY:

0.151

AC XY:

9062

AN XY:

59864

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.0980

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.194

AC:

123121

AN:

635166

Hom.:

14310

Cov.:

AF XY:

0.191

AC XY:

61204

AN XY:

320558

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.294

AC:

12717

AN:

43262

Hom.:

1901

Cov.:

AF XY:

0.279

AC XY:

5741

AN XY:

20610

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.280

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.124

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.9

DANN

Benign

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over