rs1127354
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1
The NM_033453.4(ITPA):c.94C>A(p.Pro32Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0751 in 1,613,804 control chromosomes in the GnomAD database, including 5,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★). Synonymous variant affecting the same amino acid position (i.e. P32P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.064 ( 387 hom., cov: 32)
Exomes 𝑓: 0.076 ( 4730 hom. )
Consequence
ITPA
NM_033453.4 missense
NM_033453.4 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: 6.18
Genes affected
ITPA (HGNC:6176): (inosine triphosphatase) This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.001791209).
BP6
Variant 20-3213196-C-A is Benign according to our data. Variant chr20-3213196-C-A is described in ClinVar as [drug_response]. Clinvar id is 14746.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, drug_response=1, Benign=2}.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPA | NM_033453.4 | c.94C>A | p.Pro32Thr | missense_variant | 2/8 | ENST00000380113.8 | NP_258412.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPA | ENST00000380113.8 | c.94C>A | p.Pro32Thr | missense_variant | 2/8 | 1 | NM_033453.4 | ENSP00000369456 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0643 AC: 9779AN: 152138Hom.: 389 Cov.: 32
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GnomAD3 exomes AF: 0.0752 AC: 18912AN: 251492Hom.: 971 AF XY: 0.0788 AC XY: 10708AN XY: 135920
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GnomAD4 exome AF: 0.0762 AC: 111346AN: 1461548Hom.: 4730 Cov.: 32 AF XY: 0.0776 AC XY: 56419AN XY: 727094
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GnomAD4 genome AF: 0.0642 AC: 9777AN: 152256Hom.: 387 Cov.: 32 AF XY: 0.0644 AC XY: 4793AN XY: 74438
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268
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ClinVar
Significance: drug response
Submissions summary: Benign:3Other:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Inosine triphosphatase deficiency Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Affects, no assertion criteria provided | literature only | OMIM | Sep 25, 2009 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | This variant is associated with the following publications: (PMID: 17113761, 22060550, 22613675, 19914375, 24621321, 23528839, 19631656, 25525159, 22939045, 20173735, 21659334, 19682085, 23547827, 20547162, 20637204, 12384777, 27703193, 26394463, 30106365, 19579612) - |
peginterferon alfa-2b and ribavirin response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 2B: Variants in Level 2B clinical annotations are not in PharmGKB’s Tier 1 VIPs. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2B clinical annotations must be supported by at least two independent publications. Drug-variant association: Toxicity |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
P;P;P
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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