Variant rs9547952 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006475.3(POSTN):c.2440G>A(p.Val814Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,591,826 control chromosomes in the GnomAD database, including 3,789 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.084 ( 659 hom., cov: 28)

Exomes 𝑓: 0.060 ( 3130 hom. )

Consequence

POSTN
NM_006475.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Variant links:

Genes affected

POSTN (HGNC:16953): (periostin) This gene encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. The encoded protein binds to integrins to support adhesion and migration of epithelial cells. This protein plays a role in cancer stem cell maintenance and metastasis. Mice lacking this gene exhibit cardiac valve disease, and skeletal and dental defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

POSTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001568079).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POSTN	NM_006475.3 linkuse as main transcript	c.2440G>A	p.Val814Met	missense_variant	22/23	ENST00000379747.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POSTN	ENST00000379747.9 linkuse as main transcript	c.2440G>A	p.Val814Met	missense_variant	22/23	1	NM_006475.3	P3	Q15063-1

Frequencies

GnomAD3 genomes

AF:

0.0845

AC:

12807

AN:

151622

Hom.:

659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.0719

Gnomad EAS

AF:

0.0710

Gnomad SAS

AF:

0.0609

Gnomad FIN

AF:

0.0772

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0887

GnomAD3 exomes

AF:

0.0792

AC:

19596

AN:

247524

Hom.:

1016

AF XY:

0.0748

AC XY:

10019

AN XY:

133928

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0701

Gnomad EAS exome

AF:

0.0751

Gnomad SAS exome

AF:

0.0585

Gnomad FIN exome

AF:

0.0741

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0796

GnomAD4 exome

AF:

0.0596

AC:

85793

AN:

1440086

Hom.:

3130

Cov.:

AF XY:

0.0592

AC XY:

42456

AN XY:

717232

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.0690

Gnomad4 EAS exome

AF:

0.0677

Gnomad4 SAS exome

AF:

0.0574

Gnomad4 FIN exome

AF:

0.0743

Gnomad4 NFE exome

AF:

0.0520

Gnomad4 OTH exome

AF:

0.0645

GnomAD4 genome

AF:

0.0845

AC:

12817

AN:

151740

Hom.:

659

Cov.:

AF XY:

0.0861

AC XY:

6383

AN XY:

74132

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.0719

Gnomad4 EAS

AF:

0.0712

Gnomad4 SAS

AF:

0.0616

Gnomad4 FIN

AF:

0.0772

Gnomad4 NFE

AF:

0.0568

Gnomad4 OTH

AF:

0.0878

Alfa

AF:

0.0626

Hom.:

808

Bravo

AF:

0.0894

TwinsUK

AF:

0.0512

AC:

190

ALSPAC

AF:

0.0568

AC:

219

ESP6500AA

AF:

0.121

AC:

535

ESP6500EA

AF:

0.0591

AC:

508

ExAC

AF:

0.0764

AC:

9280

Asia WGS

AF:

0.0610

AC:

215

AN:

3470

EpiCase

AF:

0.0563

EpiControl

AF:

0.0536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

.;T;.;T;.;.

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

D;D;D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.9

.;.;.;L;.;.

MutationTaster

Benign

0.91

P;P;P;P;P;P

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.53

N;N;N;N;N;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.0040

D;D;D;D;D;T

Sift4G

Uncertain

0.0050

D;D;D;D;D;D

Polyphen

0.16

B;.;.;B;.;P

Vest4

0.23

MPC

0.16

ClinPred

0.023

GERP RS

5.2

Varity_R

0.083

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over