13-37564552-C-T

Variant names:

• chr13-37564552-C-T
• rs9547952
• NM_006475.3:c.2440G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 20 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2440G>A	p.Val814Met	missense_variant	Exon 22 of 23	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2440G>A	p.Val814Met	missense_variant	Exon 22 of 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

GnomAD2 exomes AF: 0.0792 AC: 19596 AN: 247524 AF XY: 0.0748

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 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

African (AFR) AF: 0.115 AC: 3775 AN: 32818

American (AMR) AF: 0.167 AC: 7339 AN: 43872

Ashkenazi Jewish (ASJ) AF: 0.0690 AC: 1791 AN: 25942

East Asian (EAS) AF: 0.0677 AC: 2664 AN: 39350

South Asian (SAS) AF: 0.0574 AC: 4855 AN: 84596

European-Finnish (FIN) AF: 0.0743 AC: 3953 AN: 53190

Middle Eastern (MID) AF: 0.102 AC: 581 AN: 5718

European-Non Finnish (NFE) AF: 0.0520 AC: 56988 AN: 1094946

Other (OTH) AF: 0.0645 AC: 3847 AN: 59654

GnomAD4 genome AF: 0.0845 AC: 12817 AN: 151740 Hom.: 659 Cov.: 28 AF XY: 0.0861 AC XY: 6383 AN XY: 74132

African (AFR) AF: 0.116 AC: 4789 AN: 41418

American (AMR) AF: 0.144 AC: 2198 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 249 AN: 3464

East Asian (EAS) AF: 0.0712 AC: 367 AN: 5158

South Asian (SAS) AF: 0.0616 AC: 297 AN: 4824

European-Finnish (FIN) AF: 0.0772 AC: 814 AN: 10550

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3846 AN: 67760

Other (OTH) AF: 0.0878 AC: 185 AN: 2108

Alfa AF: 0.0654 Hom.: 1646

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;.;.
PhyloP100		1.8
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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