20-3209564-T-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001324236.2(ITPA):c.-328T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
ITPA
NM_001324236.2 5_prime_UTR_premature_start_codon_gain
NM_001324236.2 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.563
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 20-3209564-T-C is Benign according to our data. Variant chr20-3209564-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2161532.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPA | NM_033453.4 | c.13T>C | p.Leu5Leu | synonymous_variant | 1/8 | ENST00000380113.8 | NP_258412.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPA | ENST00000380113.8 | c.13T>C | p.Leu5Leu | synonymous_variant | 1/8 | 1 | NM_033453.4 | ENSP00000369456.3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151872Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251038Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135772
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461386Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727032
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151872Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74146
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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 | Labcorp Genetics (formerly Invitae), Labcorp | May 16, 2023 | - - |
Computational scores
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Benign
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at