chr9-76107280-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_001372043.1(PCSK5):c.1137G>A(p.Thr379=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,613,582 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 10 hom. )
Consequence
PCSK5
NM_001372043.1 synonymous
NM_001372043.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.107
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 9-76107280-G-A is Benign according to our data. Variant chr9-76107280-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037377.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.107 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK5 | NM_001372043.1 | c.1137G>A | p.Thr379= | synonymous_variant | 9/38 | ENST00000674117.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK5 | ENST00000674117.1 | c.1137G>A | p.Thr379= | synonymous_variant | 9/38 | NM_001372043.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00203 AC: 309AN: 152106Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00226 AC: 568AN: 250970Hom.: 0 AF XY: 0.00228 AC XY: 309AN XY: 135680
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GnomAD4 exome AF: 0.00331 AC: 4834AN: 1461358Hom.: 10 Cov.: 30 AF XY: 0.00329 AC XY: 2389AN XY: 726990
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GnomAD4 genome ? AF: 0.00203 AC: 309AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.00203 AC XY: 151AN XY: 74428
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PCSK5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Benign
Cadd
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Dann
Benign
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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