Variant rs8029797 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000611716.5(PCSK6):c.1858+242A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 356,284 control chromosomes in the GnomAD database, including 28,071 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 0.40 ( 13636 hom., cov: 32)

Exomes 𝑓: 0.36 ( 14435 hom. )

Consequence

PCSK6
ENST00000611716.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Variant links:

Genes affected

PCSK6 (HGNC:8569): (proprotein convertase subtilisin/kexin type 6) 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 and sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]

PCSK6 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCSK6	NM_002570.5 linkuse as main transcript	c.1858+242A>T		intron_variant		ENST00000611716.5	NP_002561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCSK6	ENST00000611716.5 linkuse as main transcript	c.1858+242A>T		intron_variant		1	NM_002570.5	ENSP00000482760	A2	P29122-1

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61202

AN:

151860

Hom.:

13603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.376

GnomAD4 exome

AF:

0.357

AC:

72999

AN:

204306

Hom.:

14435

Cov.:

AF XY:

0.351

AC XY:

36786

AN XY:

104856

show subpopulations

Gnomad4 AFR exome

AF:

0.568

Gnomad4 AMR exome

AF:

0.577

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.602

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.328

Gnomad4 OTH exome

AF:

0.364

GnomAD4 genome

AF:

0.403

AC:

61295

AN:

151978

Hom.:

13636

Cov.:

AF XY:

0.400

AC XY:

29714

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.559

Gnomad4 AMR

AF:

0.512

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.577

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.373

Alfa

AF:

0.346

Hom.:

1216

Bravo

AF:

0.439

Asia WGS

AF:

0.358

AC:

1249

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.10

DANN

Benign

0.76

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