rs10521468
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1
The NM_001372043.1(PCSK5):c.2301C>T(p.Cys767=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,610,410 control chromosomes in the GnomAD database, including 26,664 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 0.15 ( 1840 hom., cov: 32)
Exomes 𝑓: 0.18 ( 24824 hom. )
Consequence
PCSK5
NM_001372043.1 synonymous
NM_001372043.1 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.868
Genes affected
PCSK5 (HGNC:8747): (proprotein convertase subtilisin/kexin type 5) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER. It then sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. This encoded protein is widely expressed and one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It mediates posttranslational endoproteolytic processing for several integrin alpha subunits and is thought to process prorenin, pro-membrane type-1 matrix metalloproteinase and HIV-1 glycoprotein gp160. Alternative splicing results in multiple transcript variants, some of which encode distinct isoforms, including a protease packaged into dense core granules (PC5A) and a type 1 membrane bound protease (PC5B). [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP7
?
Synonymous conserved (PhyloP=0.868 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK5 | NM_001372043.1 | c.2301C>T | p.Cys767= | synonymous_variant | 18/38 | ENST00000674117.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK5 | ENST00000674117.1 | c.2301C>T | p.Cys767= | synonymous_variant | 18/38 | NM_001372043.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.145 AC: 22070AN: 151980Hom.: 1837 Cov.: 32
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GnomAD3 exomes AF: 0.144 AC: 36165AN: 251096Hom.: 3078 AF XY: 0.147 AC XY: 19986AN XY: 135690
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GnomAD4 exome AF: 0.176 AC: 257299AN: 1458312Hom.: 24824 Cov.: 31 AF XY: 0.174 AC XY: 126569AN XY: 725678
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GnomAD4 genome ? AF: 0.145 AC: 22082AN: 152098Hom.: 1840 Cov.: 32 AF XY: 0.144 AC XY: 10687AN XY: 74340
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Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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