Variant 9-136428859-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.*816A>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 0.396 in 152,382 control chromosomes in the GnomAD database, including 12,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12228 hom., cov: 32)

Exomes 𝑓: 0.33 ( 21 hom. )

Consequence

INPP5E
NM_019892.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.21

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=-0.91).

BP6

Variant 9-136428859-T-C is Benign according to our data. Variant chr9-136428859-T-C is described in ClinVar as [Benign]. Clinvar id is 365868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
INPP5E	NM_019892.6 linkuse as main transcript	c.*816A>G	3_prime_UTR_variant	10/10	ENST00000371712.4	NP_063945.2	Q9NRR6-1
INPP5E	NM_001318502.2 linkuse as main transcript	c.*816A>G	3_prime_UTR_variant	10/10		NP_001305431.1	Q9NRR6
INPP5E	XM_017014926.2 linkuse as main transcript	c.*895A>G	3_prime_UTR_variant	10/10		XP_016870415.1
INPP5E	XM_047423603.1 linkuse as main transcript	c.*895A>G	3_prime_UTR_variant	10/10		XP_047279559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP5E	ENST00000371712 linkuse as main transcript	c.*816A>G		3_prime_UTR_variant	10/10	1	NM_019892.6	ENSP00000360777.3		Q9NRR6-1
INPP5E	ENST00000676019 linkuse as main transcript	c.*816A>G		3_prime_UTR_variant	10/10			ENSP00000501984.1		Q9NRR6-2

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60240

AN:

151968

Hom.:

12199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.328

AC:

AN:

296

Hom.:

Cov.:

AF XY:

0.317

AC XY:

AN XY:

142

show subpopulations

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.438

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.397

AC:

60318

AN:

152086

Hom.:

12228

Cov.:

AF XY:

0.390

AC XY:

29028

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.379

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.412

Hom.:

19874

Bravo

AF:

0.407

Asia WGS

AF:

0.310

AC:

1079

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Joubert syndrome 1

Benign:1

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.88

DANN

Benign

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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