Variant 9-76096137-T-G 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.1107+35T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,393,828 control chromosomes in the GnomAD database, including 75,126 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 0.29 ( 6685 hom., cov: 31)

Exomes 𝑓: 0.33 ( 68441 hom. )

Consequence

PCSK5
NM_001372043.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.913

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 (SAS) allele frequency at 95% confidence interval = 0.36 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.1107+35T>G		intron_variant		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.1107+35T>G		intron_variant			NM_001372043.1	ENSP00000500971	A2

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44390

AN:

151718

Hom.:

6675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.305

AC:

71031

AN:

233090

Hom.:

10968

AF XY:

0.309

AC XY:

38888

AN XY:

125768

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.328

AC:

407249

AN:

1241992

Hom.:

68441

Cov.:

AF XY:

0.329

AC XY:

206431

AN XY:

627800

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.362

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.316

GnomAD4 genome

AF:

0.293

AC:

44434

AN:

151836

Hom.:

6685

Cov.:

AF XY:

0.289

AC XY:

21419

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.299

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.303

Hom.:

1332

Bravo

AF:

0.286

Asia WGS

AF:

0.319

AC:

1112

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.8

DANN

Benign

0.64

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