rs797044468
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001567.4(INPPL1):c.768del(p.Glu258SerfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
INPPL1
NM_001567.4 frameshift
NM_001567.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.17
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 11-72229676-CA-C is Pathogenic according to our data. Variant chr11-72229676-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 39475.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPPL1 | NM_001567.4 | c.768del | p.Glu258SerfsTer4 | frameshift_variant | 7/28 | ENST00000298229.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPPL1 | ENST00000298229.7 | c.768del | p.Glu258SerfsTer4 | frameshift_variant | 7/28 | 1 | NM_001567.4 | P1 | |
INPPL1 | ENST00000538751.5 | c.42del | p.Glu16SerfsTer4 | frameshift_variant | 6/27 | 1 | |||
INPPL1 | ENST00000537656.1 | c.42del | p.Glu16SerfsTer4 | frameshift_variant | 3/3 | 2 | |||
INPPL1 | ENST00000540329.5 | c.27+119del | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461792Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727194
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32
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727194
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Opsismodysplasia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 10, 2013 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at