chr1-226642103-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002221.4(ITPKB):c.2269A>G(p.Thr757Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,613,794 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 3 hom. )
Consequence
ITPKB
NM_002221.4 missense
NM_002221.4 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 4.97
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014902383).
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPKB | NM_002221.4 | c.2269A>G | p.Thr757Ala | missense_variant | 5/8 | ENST00000429204.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPKB | ENST00000429204.6 | c.2269A>G | p.Thr757Ala | missense_variant | 5/8 | 5 | NM_002221.4 | P1 | |
ITPKB | ENST00000272117.8 | c.2269A>G | p.Thr757Ala | missense_variant | 5/8 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152174Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000279 AC: 70AN: 251126Hom.: 1 AF XY: 0.000214 AC XY: 29AN XY: 135730
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GnomAD4 exome AF: 0.000168 AC: 245AN: 1461620Hom.: 3 Cov.: 32 AF XY: 0.000155 AC XY: 113AN XY: 727112
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GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN 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 | Feb 22, 2023 | The c.2269A>G (p.T757A) alteration is located in exon 5 (coding exon 4) of the ITPKB gene. This alteration results from a A to G substitution at nucleotide position 2269, causing the threonine (T) at amino acid position 757 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.75
ClinPred
T
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