rs12822596
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002864.3(PZP):c.3370-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,566,490 control chromosomes in the GnomAD database, including 70,369 homozygotes. 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 0.25 ( 5626 hom., cov: 32)
Exomes 𝑓: 0.30 ( 64743 hom. )
Consequence
PZP
NM_002864.3 intron
NM_002864.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.18
Genes affected
PZP (HGNC:9750): (PZP alpha-2-macroglobulin like) The protein encoded by this gene is highly expressed in late-pregnancy serum and is similar in structure to alpha-2-macroglobulin. The encoded protein, which acts as a homotetramer, inhibits the activity of all four classes of proteinases. This protein contains cleavage sites for several proteinases. Upon binding of a proteinase, the conformation of this protein changes to trap the proteinase, limiting its activity. This protein appears to be elevated in the sera of presymptomatic Alzheimer's disease patients. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PZP | NM_002864.3 | c.3370-44C>T | intron_variant | ENST00000261336.7 | NP_002855.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PZP | ENST00000261336.7 | c.3370-44C>T | intron_variant | 1 | NM_002864.3 | ENSP00000261336 | P1 | |||
PZP | ENST00000535230.5 | c.*2839-44C>T | intron_variant, NMD_transcript_variant | 1 | ENSP00000440811 |
Frequencies
GnomAD3 genomes AF: 0.255 AC: 38710AN: 152002Hom.: 5621 Cov.: 32
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GnomAD3 exomes AF: 0.273 AC: 62820AN: 230300Hom.: 9500 AF XY: 0.270 AC XY: 33896AN XY: 125324
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GnomAD4 exome AF: 0.296 AC: 418624AN: 1414370Hom.: 64743 Cov.: 27 AF XY: 0.293 AC XY: 205169AN XY: 700908
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GnomAD4 genome AF: 0.255 AC: 38740AN: 152120Hom.: 5626 Cov.: 32 AF XY: 0.256 AC XY: 19064AN XY: 74368
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at