Variant 15-101322570-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002570.5(PCSK6):c.2415A>G(p.Lys805=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,613,770 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 8 hom. )

Consequence

PCSK6
NM_002570.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0420

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 15-101322570-T-C is Benign according to our data. Variant chr15-101322570-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 789334.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.042 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PCSK6	NM_002570.5 linkuse as main transcript	c.2415A>G	p.Lys805=	synonymous_variant	18/22	ENST00000611716.5	NP_002561.1
PCSK6	NM_138319.4 linkuse as main transcript	c.2376A>G	p.Lys792=	synonymous_variant	17/21		NP_612192.1
PCSK6	NM_001291309.2 linkuse as main transcript	c.2193A>G	p.Lys731=	synonymous_variant	16/20		NP_001278238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCSK6	ENST00000611716.5 linkuse as main transcript	c.2415A>G	p.Lys805=	synonymous_variant	18/22	1	NM_002570.5	ENSP00000482760	A2	P29122-1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

381

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00420

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00275

AC:

685

AN:

249098

Hom.:

AF XY:

0.00272

AC XY:

368

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.000775

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00376

Gnomad NFE exome

AF:

0.00486

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00350

AC:

5111

AN:

1461482

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2470

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00455

Gnomad4 NFE exome

AF:

0.00415

Gnomad4 OTH exome

AF:

0.00331

GnomAD4 genome

AF:

0.00250

AC:

381

AN:

152288

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00420

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.00227

EpiCase

AF:

0.00218

EpiControl

AF:

0.00332

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.4

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over