chr9-76107298-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001372043.1(PCSK5):c.1155G>A(p.Thr385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,613,868 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 2 hom. )
Consequence
PCSK5
NM_001372043.1 synonymous
NM_001372043.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.65
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=-0.6).
BP6
Variant 9-76107298-G-A is Benign according to our data. Variant chr9-76107298-G-A is described in ClinVar as [Benign]. Clinvar id is 711510.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.65 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK5 | NM_001372043.1 | c.1155G>A | p.Thr385= | synonymous_variant | 9/38 | ENST00000674117.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK5 | ENST00000674117.1 | c.1155G>A | p.Thr385= | synonymous_variant | 9/38 | NM_001372043.1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00214 AC: 326AN: 152136Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000713 AC: 179AN: 251058Hom.: 0 AF XY: 0.000634 AC XY: 86AN XY: 135712
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GnomAD4 exome AF: 0.000310 AC: 453AN: 1461614Hom.: 2 Cov.: 30 AF XY: 0.000327 AC XY: 238AN XY: 727108
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GnomAD4 genome AF: 0.00213 AC: 325AN: 152254Hom.: 1 Cov.: 33 AF XY: 0.00234 AC XY: 174AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2018 | - - |
Computational scores
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Benign
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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