rs9547952

Positions:

• chr13-37564552-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 (HGNC:):

ACMG classification

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	Protein	UniProt
POSTN	NM_006475.3	c.2440G>A	p.Val814Met	missense_variant	22/23	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2440G>A	p.Val814Met	missense_variant	22/23	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12807 AN: 151622 Hom.: 659 Cov.: 28

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

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.: 26 AF XY: 0.0592 AC XY: 42456 AN XY: 717232

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.: 28 AF XY: 0.0861 AC XY: 6383 AN XY: 74132

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	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	.;T;.;T;.;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.84	D
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	T
MutationAssessor	Benign	1.9	.;.;.;L;.;.
PrimateAI	Benign	0.45	T
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	T
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

Other links and lift over

dbSNP: rs9547952; hg19: chr13-38138689; COSMIC: COSV65713076; COSMIC: COSV65713076;