rs183325660
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_033453.4(ITPA):āc.567T>Cā(p.Phe189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,612,850 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 33)
Exomes š: 0.000072 ( 1 hom. )
Consequence
ITPA
NM_033453.4 synonymous
NM_033453.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.118
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 20-3223444-T-C is Benign according to our data. Variant chr20-3223444-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 464836.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.118 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000788 (12/152374) while in subpopulation EAS AF= 0.00231 (12/5192). AF 95% confidence interval is 0.00133. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPA | NM_033453.4 | c.567T>C | p.Phe189= | synonymous_variant | 8/8 | ENST00000380113.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPA | ENST00000380113.8 | c.567T>C | p.Phe189= | synonymous_variant | 8/8 | 1 | NM_033453.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152256Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000121 AC: 30AN: 248880Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134634
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GnomAD4 exome AF: 0.0000719 AC: 105AN: 1460476Hom.: 1 Cov.: 31 AF XY: 0.0000771 AC XY: 56AN XY: 726424
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152374Hom.: 0 Cov.: 33 AF XY: 0.0000939 AC XY: 7AN XY: 74518
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inosine triphosphatase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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