Variant chr15-101489563-G-GGCGCCCCCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_002570.5(PCSK6):c.107_108insGGGGGGCGC(p.Ala36_Gly38dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 968,222 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 28)

Exomes 𝑓: 0.00053 ( 2 hom. )

Consequence

PCSK6
NM_002570.5 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07

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 Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_002570.5.

BP6

Variant 15-101489563-G-GGCGCCCCCC is Benign according to our data. Variant chr15-101489563-G-GGCGCCCCCC is described in ClinVar as [Likely_benign]. Clinvar id is 2645757.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK6	NM_002570.5 linkuse as main transcript	c.107_108insGGGGGGCGC	p.Ala36_Gly38dup	inframe_insertion	1/22	ENST00000611716.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK6	ENST00000611716.5 linkuse as main transcript	c.107_108insGGGGGGCGC	p.Ala36_Gly38dup	inframe_insertion	1/22	1	NM_002570.5	A2	P29122-1

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

216

AN:

142596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000684

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00705

Gnomad ASJ

AF:

0.00541

Gnomad EAS

AF:

0.00368

Gnomad SAS

AF:

0.00129

Gnomad FIN

AF:

0.000372

Gnomad MID

AF:

0.00714

Gnomad NFE

AF:

0.000540

Gnomad OTH

AF:

0.00307

GnomAD4 exome

AF:

0.000529

AC:

437

AN:

825642

Hom.:

Cov.:

AF XY:

0.000543

AC XY:

207

AN XY:

381498

show subpopulations

Gnomad4 AFR exome

AF:

0.000381

Gnomad4 AMR exome

AF:

0.00677

Gnomad4 ASJ exome

AF:

0.00361

Gnomad4 EAS exome

AF:

0.00114

Gnomad4 SAS exome

AF:

0.000304

Gnomad4 FIN exome

AF:

0.00175

Gnomad4 NFE exome

AF:

0.000492

Gnomad4 OTH exome

AF:

0.000928

GnomAD4 genome

AF:

0.00151

AC:

216

AN:

142580

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

116

AN XY:

69284

show subpopulations

Gnomad4 AFR

AF:

0.000683

Gnomad4 AMR

AF:

0.00698

Gnomad4 ASJ

AF:

0.00541

Gnomad4 EAS

AF:

0.00370

Gnomad4 SAS

AF:

0.00151

Gnomad4 FIN

AF:

0.000372

Gnomad4 NFE

AF:

0.000540

Gnomad4 OTH

AF:

0.00306

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

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

PCSK6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

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