rs3830384

Variant names:

• chr9-76189290-G-GAAAAT
• rs3830384
• NM_001372043.1:c.2510+70_2510+74dupAATAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001372043.1(PCSK5):​c.2510+70_2510+74dupAATAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,323,028 control chromosomes in the GnomAD database, including 68,348 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7372 hom., cov: 17)
  • Exomes 𝑓: 0.31 (60976 hom.)
• Consequence: PCSK5 NM_001372043.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK5	NM_001372043.1	c.2510+70_2510+74dupAATAA		intron_variant	Intron 19 of 37	ENST00000674117.1	NP_001358972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK5	ENST00000674117.1	c.2510+67_2510+68insAAAAT		intron_variant	Intron 19 of 37		NM_001372043.1	ENSP00000500971.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45744 AN: 151724 Hom.: 7368 Cov.: 17

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.307 AC: 359946 AN: 1171184 Hom.: 60976 AF XY: 0.309 AC XY: 183087 AN XY: 593410

African (AFR) AF: 0.185 AC: 5020 AN: 27076

American (AMR) AF: 0.431 AC: 14951 AN: 34654

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 6158 AN: 21654

East Asian (EAS) AF: 0.566 AC: 21477 AN: 37942

South Asian (SAS) AF: 0.348 AC: 25284 AN: 72736

European-Finnish (FIN) AF: 0.290 AC: 13412 AN: 46242

Middle Eastern (MID) AF: 0.319 AC: 1105 AN: 3464

European-Non Finnish (NFE) AF: 0.293 AC: 256818 AN: 877340

Other (OTH) AF: 0.314 AC: 15721 AN: 50076

GnomAD4 genome AF: 0.301 AC: 45760 AN: 151844 Hom.: 7372 Cov.: 17 AF XY: 0.305 AC XY: 22665 AN XY: 74204

African (AFR) AF: 0.203 AC: 8420 AN: 41476

American (AMR) AF: 0.380 AC: 5795 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3466

East Asian (EAS) AF: 0.591 AC: 3035 AN: 5134

South Asian (SAS) AF: 0.355 AC: 1708 AN: 4812

European-Finnish (FIN) AF: 0.308 AC: 3243 AN: 10520

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21288 AN: 67892

Other (OTH) AF: 0.324 AC: 683 AN: 2110

Alfa AF: 0.314 Hom.: 817

Asia WGS AF: 0.477 AC: 1658 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3830384; hg19: chr9-78804206;