Variant rs7020560 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001372043.1(PCSK5):c.48G>A(p.Leu16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,518,016 control chromosomes in the GnomAD database, including 6,709 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 0.13 ( 2348 hom., cov: 33)

Exomes 𝑓: 0.069 ( 4361 hom. )

Consequence

PCSK5
NM_001372043.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.855

Variant links:

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]

PCSK5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=0.855 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK5	NM_001372043.1 linkuse as main transcript	c.48G>A	p.Leu16=	synonymous_variant	1/38	ENST00000674117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK5	ENST00000674117.1 linkuse as main transcript	c.48G>A	p.Leu16=	synonymous_variant	1/38		NM_001372043.1	A2
PCSK5	ENST00000376752.9 linkuse as main transcript	c.48G>A	p.Leu16=	synonymous_variant	1/21	1			Q92824-2
PCSK5	ENST00000545128.5 linkuse as main transcript	c.48G>A	p.Leu16=	synonymous_variant	1/37	5		P4	Q92824-1
PCSK5	ENST00000376767.7 linkuse as main transcript	n.560G>A		non_coding_transcript_exon_variant	1/14	2

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19875

AN:

152072

Hom.:

2345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0703

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.000776

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.0908

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.0713

AC:

11845

AN:

166054

Hom.:

809

AF XY:

0.0658

AC XY:

6101

AN XY:

92710

show subpopulations

Gnomad AFR exome

AF:

0.307

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.0220

Gnomad FIN exome

AF:

0.0882

Gnomad NFE exome

AF:

0.0652

Gnomad OTH exome

AF:

0.0726

GnomAD4 exome

AF:

0.0686

AC:

93668

AN:

1365826

Hom.:

4361

Cov.:

AF XY:

0.0668

AC XY:

45174

AN XY:

676764

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.0451

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.0849

Gnomad4 NFE exome

AF:

0.0670

Gnomad4 OTH exome

AF:

0.0734

GnomAD4 genome

AF:

0.131

AC:

19886

AN:

152190

Hom.:

2348

Cov.:

AF XY:

0.129

AC XY:

9584

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.0702

Gnomad4 ASJ

AF:

0.0470

Gnomad4 EAS

AF:

0.000973

Gnomad4 SAS

AF:

0.0217

Gnomad4 FIN

AF:

0.0908

Gnomad4 NFE

AF:

0.0651

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0888

Hom.:

404

Bravo

AF:

0.138

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over