15-101481014-G-C

Variant names:

• chr15-101481014-G-C
• rs7165901
• NM_002570.5:c.297+8360C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002570.5(PCSK6):​c.297+8360C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,158 control chromosomes in the GnomAD database, including 1,639 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 0.14 (1639 hom., cov: 33)
• Consequence: PCSK6 NM_002570.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 1 publications found

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]

LOC124903566 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCSK6	NM_002570.5	c.297+8360C>G		intron_variant	Intron 1 of 21	ENST00000611716.5	NP_002561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCSK6	ENST00000611716.5	c.297+8360C>G		intron_variant	Intron 1 of 21	1	NM_002570.5	ENSP00000482760.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20596 AN: 152040 Hom.: 1630 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.135

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20633 AN: 152158 Hom.: 1639 Cov.: 33 AF XY: 0.141 AC XY: 10456 AN XY: 74388

African (AFR) AF: 0.143 AC: 5935 AN: 41486

American (AMR) AF: 0.155 AC: 2376 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3472

East Asian (EAS) AF: 0.351 AC: 1814 AN: 5172

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4820

European-Finnish (FIN) AF: 0.120 AC: 1269 AN: 10600

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7162 AN: 68008

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.0479 Hom.: 30

Bravo AF: 0.138

Asia WGS AF: 0.293 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.78
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7165901; hg19: chr15-102021219;