Variant 9-76159037-G-A 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.1485G>A(p.Ser495=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,613,712 control chromosomes in the GnomAD database, including 52,619 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 0.23 ( 4445 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48174 hom. )

Consequence

PCSK5
NM_001372043.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

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=-0.65).

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCSK5	NM_001372043.1 linkuse as main transcript	c.1485G>A	p.Ser495=	synonymous_variant	12/38	ENST00000674117.1	NP_001358972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCSK5	ENST00000674117.1 linkuse as main transcript	c.1485G>A	p.Ser495=	synonymous_variant	12/38		NM_001372043.1	ENSP00000500971	A2

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35566

AN:

151924

Hom.:

4435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.253

GnomAD3 exomes

AF:

0.268

AC:

67291

AN:

251160

Hom.:

10158

AF XY:

0.263

AC XY:

35673

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.450

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.324

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.251

AC:

367232

AN:

1461670

Hom.:

48174

Cov.:

AF XY:

0.251

AC XY:

182568

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.359

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.194

Gnomad4 NFE exome

AF:

0.244

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.234

AC:

35590

AN:

152042

Hom.:

4445

Cov.:

AF XY:

0.236

AC XY:

17514

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.237

Hom.:

8794

Bravo

AF:

0.242

Asia WGS

AF:

0.332

AC:

1154

AN:

3478

EpiCase

AF:

0.236

EpiControl

AF:

0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.3

DANN

Benign

0.71

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