Variant 11-117208910-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004716.4(PCSK7):c.1678C>G(p.Arg560Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCSK7
NM_004716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

PCSK7 (HGNC:8748): (proprotein convertase subtilisin/kexin type 7) 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. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene has been implicated in the transcriptional regulation of housekeeping genes and plays a role in the regulation of iron metabolism. A t(11;14)(q23;q32) chromosome translocation associated with B-cell lymphoma occurs between this gene and its inverted counterpart. [provided by RefSeq, Feb 2014]

PCSK7 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042326003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK7	NM_004716.4 linkuse as main transcript	c.1678C>G	p.Arg560Gly	missense_variant	13/17	ENST00000320934.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCSK7	ENST00000320934.8 linkuse as main transcript	c.1678C>G	p.Arg560Gly	missense_variant	13/17	1	NM_004716.4	P1
	ENST00000624094.1 linkuse as main transcript	n.3944G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149318

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.000295

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00109

Gnomad FIN

AF:

0.000193

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000209

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00151

AC:

361

AN:

238570

Hom.:

AF XY:

0.00162

AC XY:

209

AN XY:

128694

show subpopulations

Gnomad AFR exome

AF:

0.00170

Gnomad AMR exome

AF:

0.000536

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.00299

Gnomad SAS exome

AF:

0.00259

Gnomad FIN exome

AF:

0.00191

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00136

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000458

AC:

655

AN:

1428628

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

326

AN XY:

710752

show subpopulations

Gnomad4 AFR exome

AF:

0.000426

Gnomad4 AMR exome

AF:

0.000228

Gnomad4 ASJ exome

AF:

0.000705

Gnomad4 EAS exome

AF:

0.000804

Gnomad4 SAS exome

AF:

0.000950

Gnomad4 FIN exome

AF:

0.000382

Gnomad4 NFE exome

AF:

0.000420

Gnomad4 OTH exome

AF:

0.000356

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000241

AC:

AN:

149440

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

AN XY:

73006

show subpopulations

Gnomad4 AFR

AF:

0.000270

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.000295

Gnomad4 EAS

AF:

0.000201

Gnomad4 SAS

AF:

0.00109

Gnomad4 FIN

AF:

0.000193

Gnomad4 NFE

AF:

0.000209

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00236

Hom.:

ExAC

AF:

0.0118

AC:

1435

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Skin tags;C1333160:Pericallosal lipoma;C4022007:Midline facial cleft

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.042

T;T

MetaSVM

Uncertain

0.011

MutationAssessor

Pathogenic

4.2

H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.3

D;.

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0020

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.91

MPC

1.6

ClinPred

0.13

GERP RS

3.8

Varity_R

0.74

gMVP

0.87

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over