11-72224999-CGGGGCGCCGGGCCCGG-CGGGGCGCCGGGCCCGGGGGGCGCCGGGCCCGG

Variant names:

• chr11-72224999-C-CGGGGCGCCGGGCCCGG
• NM_001567.4:c.24_39dupGGGCCCGGGGGGCGCC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001567.4(INPPL1):​c.24_39dupGGGCCCGGGGGGCGCC​(p.Leu14GlyfsTer66) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INPPL1 NM_001567.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.989 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPPL1	NM_001567.4	c.24_39dupGGGCCCGGGGGGCGCC	p.Leu14GlyfsTer66	frameshift_variant	Exon 1 of 28	ENST00000298229.7	NP_001558.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPPL1	ENST00000298229.7	c.24_39dupGGGCCCGGGGGGCGCC	p.Leu14GlyfsTer66	frameshift_variant	Exon 1 of 28	1	NM_001567.4	ENSP00000298229.2
INPPL1	ENST00000540973.1	c.24_39dupGGGCCCGGGGGGCGCC	p.Leu14GlyfsTer14	frameshift_variant	Exon 2 of 2	3		ENSP00000440904.1
INPPL1	ENST00000543234.1	c.24_39dupGGGCCCGGGGGGCGCC	p.Leu14GlyfsTer10	frameshift_variant	Exon 2 of 2	2		ENSP00000440512.1
INPPL1	ENST00000541544.1	n.-70_-69insGGGGCGCCGGGCCCGG		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71936043;