1-226735553-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_002221.4(ITPKB):c.1906A>G(p.Thr636Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000519 in 1,540,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T636I) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Consequence
ITPKB
NM_002221.4 missense
NM_002221.4 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 3.64
Genes affected
ITPKB (HGNC:6179): (inositol-trisphosphate 3-kinase B) The protein encoded by this protein regulates inositol phosphate metabolism by phosphorylation of second messenger inositol 1,4,5-trisphosphate to Ins(1,3,4,5)P4. The activity of this encoded protein is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling. Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPKB | NM_002221.4 | c.1906A>G | p.Thr636Ala | missense_variant | 2/8 | ENST00000429204.6 | |
ITPKB | NM_001388404.1 | c.1906A>G | p.Thr636Ala | missense_variant | 2/3 | ||
ITPKB | XM_017001211.3 | c.1906A>G | p.Thr636Ala | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPKB | ENST00000429204.6 | c.1906A>G | p.Thr636Ala | missense_variant | 2/8 | 5 | NM_002221.4 | P1 | |
ITPKB | ENST00000272117.8 | c.1906A>G | p.Thr636Ala | missense_variant | 2/8 | 1 | P1 | ||
ITPKB | ENST00000366784.1 | c.1906A>G | p.Thr636Ala | missense_variant | 2/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000504 AC: 7AN: 1388598Hom.: 0 Cov.: 31 AF XY: 0.00000585 AC XY: 4AN XY: 683264
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 10, 2023 | The c.1906A>G (p.T636A) alteration is located in exon 2 (coding exon 1) of the ITPKB gene. This alteration results from a A to G substitution at nucleotide position 1906, causing the threonine (T) at amino acid position 636 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;D
Polyphen
D;D;.
Vest4
MutPred
Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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