15-101499466-G-C

Variant summary

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

The ENST00000557794.5(PCSK6):​n.123+25614C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,872 control chromosomes in the GnomAD database, including 10,380 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 0.37 ( 10380 hom., cov: 31)

Consequence

PCSK6
ENST00000557794.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.363
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]

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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=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCSK6ENST00000557794.5 linkn.123+25614C>G intron_variant Intron 1 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.369
AC:
55935
AN:
151754
Hom.:
10379
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.353
Gnomad AMI
AF:
0.484
Gnomad AMR
AF:
0.423
Gnomad ASJ
AF:
0.304
Gnomad EAS
AF:
0.476
Gnomad SAS
AF:
0.381
Gnomad FIN
AF:
0.306
Gnomad MID
AF:
0.370
Gnomad NFE
AF:
0.368
Gnomad OTH
AF:
0.372
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.369
AC:
55965
AN:
151872
Hom.:
10380
Cov.:
31
AF XY:
0.367
AC XY:
27252
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.353
Gnomad4 AMR
AF:
0.423
Gnomad4 ASJ
AF:
0.304
Gnomad4 EAS
AF:
0.475
Gnomad4 SAS
AF:
0.381
Gnomad4 FIN
AF:
0.306
Gnomad4 NFE
AF:
0.368
Gnomad4 OTH
AF:
0.370
Alfa
AF:
0.221
Hom.:
508
Bravo
AF:
0.379
Asia WGS
AF:
0.385
AC:
1340
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
3.4
DANN
Benign
0.80

Splicing

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.

Other links and lift over

dbSNP: rs8033863; hg19: chr15-102039669; API