rs878853122

Variant names:

• chr11-72225013-CG-C
• NM_001567.4:c.35delG

Your query was ambiguous. Multiple possible variants found:

• chr11-72225013-CG-C
• chr11-72225013-CG-CGG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001567.4(INPPL1):​c.35delG​(p.Gly12AlafsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000942 in 1,061,596 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: INPPL1 NM_001567.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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 10 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. There are 24 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.35delG	p.Gly12AlafsTer15	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.35delG	p.Gly12AlafsTer15	frameshift_variant	Exon 1 of 28	1	NM_001567.4	ENSP00000298229.2
INPPL1	ENST00000540973.1	c.35delG	p.Gly12AlafsTer11	frameshift_variant	Exon 2 of 2	3		ENSP00000440904.1
INPPL1	ENST00000543234.1	c.35delG	p.Gly12AlafsTer6	frameshift_variant	Exon 2 of 2	2		ENSP00000440512.1
INPPL1	ENST00000541544.1	n.-55delG		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000942 AC: 10 AN: 1061596 Hom.: 0 Cov.: 30 AF XY: 0.0000120 AC XY: 6 AN XY: 501424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000402

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000881

Gnomad4 OTH exome AF: 0.0000238

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr11-71936057;