rs71269007

chr9-136433147-G-GCGCCCACCCCCCCAGCCAchr9-136433147-G-GCGCCCACCCCTCCAchr9-136433147-G-GCGCCCACCCCTCCAGCCAchr9-136433147-G-GCGCCCACCCCTCCAGCCACGCCCACCCCTCCAGCCAchr9-136433147-G-GCGCCCACCCCTCCAGCCACGCCCACCCCTCCAGCCACGCCCACCCCTCCAGCCAchr9-136433147-G-GCGCCCACCCCTCCAGCCGCGCCCACCCCTCCAGCCAchr9-136433147-G-GCGCCCACCCCTCCAGCCGCGCCCACCCCTCCAGCCGCGCCCACCCCTCCAGCCAchr9-136433147-G-GCGCCCACCCCTCCATCCAchr9-136433147-G-GCGCCCACCCCTCTAGCCAchr9-136433147-G-GCGCCCACCCCTTCAGCCGCGCCCACCCCTCCAGCCAchr9-136433147-G-GCGCCCACCCTTCCAGCCA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019892.6(INPP5E):c.1159+7_1159+8insTGGCTGGGGGGGTGGGCG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 148,352 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 28)
• Consequence: INPP5E NM_019892.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP5E	NM_019892.6	c.1159+7_1159+8insTGGCTGGGGGGGTGGGCG		splice_region_variant, intron_variant		ENST00000371712.4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000202 AC: 3 AN: 148352 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 53

GnomAD4 genome AF: 0.0000202 AC: 3 AN: 148352 Hom.: 0 Cov.: 28 AF XY: 0.0000276 AC XY: 2 AN XY: 72392

Gnomad4 AFR AF: 0.0000515

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;