Variant 9-76189788-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001372043.1(PCSK5):c.2626+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,011,794 control chromosomes in the GnomAD database, including 8,646 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 0.15 ( 1970 hom., cov: 32)

Exomes 𝑓: 0.12 ( 6676 hom. )

Consequence

PCSK5
NM_001372043.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.399

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 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.2626+42G>A		intron_variant		ENST00000674117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK5	ENST00000674117.1 linkuse as main transcript	c.2626+42G>A		intron_variant			NM_001372043.1	A2

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

22645

AN:

147924

Hom.:

1967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.0949

Gnomad AMR

AF:

0.0957

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.0825

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.127

AC:

26136

AN:

205320

Hom.:

1700

AF XY:

0.127

AC XY:

13943

AN XY:

109616

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.0731

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.0854

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.120

AC:

103249

AN:

863752

Hom.:

6676

Cov.:

AF XY:

0.120

AC XY:

54036

AN XY:

451588

show subpopulations

Gnomad4 AFR exome

AF:

0.252

Gnomad4 AMR exome

AF:

0.0722

Gnomad4 ASJ exome

AF:

0.0884

Gnomad4 EAS exome

AF:

0.0953

Gnomad4 SAS exome

AF:

0.0962

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.153

AC:

22674

AN:

148042

Hom.:

1970

Cov.:

AF XY:

0.151

AC XY:

10945

AN XY:

72364

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.0956

Gnomad4 ASJ

AF:

0.0899

Gnomad4 EAS

AF:

0.0827

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.120

Hom.:

1442

Bravo

AF:

0.153

Asia WGS

AF:

0.111

AC:

384

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.4

DANN

Benign

0.80

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