11-117206025-G-A

Position:

chr11-117206025-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004716.4(PCSK7):c.2330C>T(p.Pro777Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,222,646 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 67 hom., cov: 30)

Exomes 𝑓: 0.028 ( 554 hom. )

Consequence

PCSK7
NM_004716.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.729

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:

TAGLN (HGNC:11553): (transgelin) This gene encodes a shape change and transformation sensitive actin-binding protein which belongs to the calponin family. It is ubiquitously expressed in vascular and visceral smooth muscle, and is an early marker of smooth muscle differentiation. The encoded protein is thought to be involved in calcium-independent smooth muscle contraction. It acts as a tumor suppressor, and the loss of its expression is an early event in cell transformation and the development of some tumors, coinciding with cellular plasticity. The encoded protein has a domain architecture consisting of an N-terminal calponin homology (CH) domain and a C-terminal calponin-like (CLIK) domain. Mice with a knockout of the orthologous gene are viable and fertile but their vascular smooth muscle cells exhibit alterations in the distribution of the actin filament and changes in cytoskeletal organization. [provided by RefSeq, Aug 2017]

TAGLN links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016633868).

BP6

Variant 11-117206025-G-A is Benign according to our data. Variant chr11-117206025-G-A is described in ClinVar as [Benign]. Clinvar id is 790849.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCSK7	NM_004716.4 linkuse as main transcript	c.2330C>T	p.Pro777Leu	missense_variant	17/17	ENST00000320934.8
TAGLN	NM_003186.5 linkuse as main transcript	c.*1666G>A		3_prime_UTR_variant	5/5	ENST00000392951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PCSK7	ENST00000320934.8 linkuse as main transcript	c.2330C>T	p.Pro777Leu	missense_variant	17/17	1	NM_004716.4	P1
TAGLN	ENST00000392951.9 linkuse as main transcript	c.*1666G>A		3_prime_UTR_variant	5/5	1	NM_003186.5	P1
	ENST00000624094.1 linkuse as main transcript	n.1059G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3542

AN:

150762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00597

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.0382

Gnomad SAS

AF:

0.0915

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0316

Gnomad OTH

AF:

0.0194

GnomAD3 exomes

AF:

0.0292

AC:

3908

AN:

133882

Hom.:

AF XY:

0.0319

AC XY:

2232

AN XY:

70032

show subpopulations

Gnomad AFR exome

AF:

0.00501

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.0362

Gnomad SAS exome

AF:

0.0826

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.0264

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0276

AC:

29528

AN:

1071766

Hom.:

554

Cov.:

AF XY:

0.0293

AC XY:

15629

AN XY:

533502

show subpopulations

Gnomad4 AFR exome

AF:

0.00408

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.0352

Gnomad4 SAS exome

AF:

0.0797

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0250

Gnomad4 OTH exome

AF:

0.0269

GnomAD4 genome

AF:

0.0235

AC:

3543

AN:

150880

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1821

AN XY:

73704

show subpopulations

Gnomad4 AFR

AF:

0.00595

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.0188

Gnomad4 EAS

AF:

0.0383

Gnomad4 SAS

AF:

0.0920

Gnomad4 FIN

AF:

0.0159

Gnomad4 NFE

AF:

0.0316

Gnomad4 OTH

AF:

0.0187

Alfa

AF:

0.0252

Hom.:

Bravo

AF:

0.0210

ESP6500AA

AF:

0.00380

AC:

ESP6500EA

AF:

0.0223

AC:

185

ExAC

AF:

0.0205

AC:

2387

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.1

DANN

Benign

0.52

DEOGEN2

Benign

0.0095

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.63

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

0.32

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.040

MPC

0.50

ClinPred

0.00097

GERP RS

1.8

Varity_R

0.017

gMVP

0.11

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