11-34916337-G-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015957.4(APIP):c.-53C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000875 in 1,599,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 36)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
APIP
NM_015957.4 5_prime_UTR
NM_015957.4 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.08
Genes affected
APIP (HGNC:17581): (APAF1 interacting protein) Enables identical protein binding activity; methylthioribulose 1-phosphate dehydratase activity; and zinc ion binding activity. Involved in several processes, including L-methionine salvage from methylthioadenosine; protein homotetramerization; and pyroptosis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
PDHX (HGNC:21350): (pyruvate dehydrogenase complex component X) The pyruvate dehydrogenase (PDH) complex is located in the mitochondrial matrix and catalyzes the conversion of pyruvate to acetyl coenzyme A. The PDH complex thereby links glycolysis to Krebs cycle. The PDH complex contains three catalytic subunits, E1, E2, and E3, two regulatory subunits, E1 kinase and E1 phosphatase, and a non-catalytic subunit, E3 binding protein (E3BP). This gene encodes the E3 binding protein subunit; also known as component X of the pyruvate dehydrogenase complex. This protein tethers E3 dimers to the E2 core of the PDH complex. Defects in this gene are a cause of pyruvate dehydrogenase deficiency which results in neurological dysfunction and lactic acidosis in infancy and early childhood. This protein is also a minor antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC eventually leads to cirrhosis and liver failure. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APIP | NM_015957.4 | c.-53C>A | 5_prime_UTR_variant | Exon 1 of 7 | ENST00000395787.4 | NP_057041.2 | ||
APIP | XM_011520154.4 | c.-97C>A | 5_prime_UTR_variant | Exon 1 of 8 | XP_011518456.1 | |||
APIP | XM_017017875.3 | c.-410C>A | 5_prime_UTR_variant | Exon 1 of 8 | XP_016873364.1 | |||
PDHX | XM_011520390.2 | c.-21+399G>T | intron_variant | Intron 1 of 10 | XP_011518692.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 36
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GnomAD3 exomes AF: 0.0000141 AC: 3AN: 212210Hom.: 0 AF XY: 0.00000858 AC XY: 1AN XY: 116506
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GnomAD4 exome AF: 0.00000622 AC: 9AN: 1447470Hom.: 0 Cov.: 48 AF XY: 0.00000417 AC XY: 3AN XY: 718842
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 36 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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ClinVar
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Name
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CADD
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DANN
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RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at