rs1060505039
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_016532.4(INPP5K):c.277A>G(p.Met93Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M93I) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
INPP5K
NM_016532.4 missense
NM_016532.4 missense
Scores
8
8
1
Clinical Significance
Conservation
PhyloP100: 5.79
Genes affected
INPP5K (HGNC:33882): (inositol polyphosphate-5-phosphatase K) This gene encodes a protein with 5-phosphatase activity toward polyphosphate inositol. The protein localizes to the cytosol in regions lacking actin stress fibers. It is thought that this protein may negatively regulate the actin cytoskeleton. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.935
PP5
?
Variant 17-1509784-T-C is Pathogenic according to our data. Variant chr17-1509784-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 417779.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5K | NM_016532.4 | c.277A>G | p.Met93Val | missense_variant | 4/12 | ENST00000421807.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5K | ENST00000421807.7 | c.277A>G | p.Met93Val | missense_variant | 4/12 | 1 | NM_016532.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
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
Congenital muscular dystrophy with cataracts and intellectual disability Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 04, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.;.;T;.;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;N
PrimateAI
Uncertain
T
REVEL
Pathogenic
Sift4G
Uncertain
D;D;D;T;.;.;D;.
Polyphen
B;.;.;.;.;.;.;.
Vest4
MutPred
Loss of sheet (P = 0.1501);.;.;.;Loss of sheet (P = 0.1501);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at