11-72225097-CGGGCCGCGATGGCA-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001567.4(INPPL1):c.115_128del(p.Gly39LeufsTer31) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INPPL1 NM_001567.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.85

Genes affected

INPPL1 (HGNC:6080): (inositol polyphosphate phosphatase like 1) The protein encoded by this gene is an SH2-containing 5'-inositol phosphatase that is involved in the regulation of insulin function. The encoded protein also plays a role in the regulation of epidermal growth factor receptor turnover and actin remodelling. Additionally, this gene supports metastatic growth in breast cancer and is a valuable biomarker for breast cancer. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-72225097-CGGGCCGCGATGGCA-C is Pathogenic according to our data. Variant chr11-72225097-CGGGCCGCGATGGCA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1683469.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPPL1	NM_001567.4	c.115_128del	p.Gly39LeufsTer31	frameshift_variant	1/28	ENST00000298229.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPPL1	ENST00000298229.7	c.115_128del	p.Gly39LeufsTer31	frameshift_variant	1/28	1	NM_001567.4	P1
INPPL1	ENST00000541544.1	n.31_44del		non_coding_transcript_exon_variant	1/3	2
INPPL1	ENST00000540973.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Opsismodysplasia Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics

Apr 01, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71936141;