chr9-136433147-G-GCGCCCACCCCTCCAGCCACGCCCACCCCTCCAGCCA

Position:

• 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.695

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]

ACMG classification

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	Protein	UniProt
INPP5E	NM_019892.6	c.1159+7_1159+8insTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCG		splice_region_variant, intron_variant		ENST00000371712.4	NP_063945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP5E	ENST00000371712.4	c.1159+7_1159+8insTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCG		splice_region_variant, intron_variant		1	NM_019892.6	ENSP00000360777	P1
INPP5E	ENST00000676019.1	c.1057+7_1057+8insTGGCTGGAGGGGTGGGCGTGGCTGGAGGGGTGGGCG		splice_region_variant, intron_variant				ENSP00000501984

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

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

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

Submissions by phenotype

Familial aplasia of the vermis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71269007; hg19: chr9-139327599;