Genetic Variant POSTN:p.Val814Leu (chr13-37564552-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006475.3(POSTN):c.2440G>C(p.Val814Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,443,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 28)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

POSTN
NM_006475.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24820316).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POSTN	NM_006475.3	MANE Select	c.2440G>C	p.Val814Leu	missense	Exon 22 of 23	NP_006466.2
POSTN	NM_001286665.2		c.2359G>C	p.Val787Leu	missense	Exon 21 of 22	NP_001273594.1
POSTN	NM_001330517.2		c.2356G>C	p.Val786Leu	missense	Exon 21 of 22	NP_001317446.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POSTN	ENST00000379747.9	TSL:1 MANE Select	c.2440G>C	p.Val814Leu	missense	Exon 22 of 23	ENSP00000369071.4
POSTN	ENST00000379743.8	TSL:1	c.2359G>C	p.Val787Leu	missense	Exon 21 of 22	ENSP00000369067.4
POSTN	ENST00000541179.5	TSL:1	c.2275G>C	p.Val759Leu	missense	Exon 20 of 21	ENSP00000437959.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1443112

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32948

American (AMR)

AF:

0.0000227

AC:

AN:

43966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39386

South Asian (SAS)

AF:

0.00

AC:

AN:

84768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097338

Other (OTH)

AF:

0.00

AC:

AN:

59758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

Eigen

Benign

0.034

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.071

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

1.9

PhyloP100

1.8

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.45

REVEL

Benign

0.27

Sift

Uncertain

0.013

Sift4G

Uncertain

0.019

Polyphen

0.077

Vest4

0.21

MutPred

0.18

Gain of helix (P = 0.0425)

MVP

0.90

MPC

0.17

ClinPred

0.79

GERP RS

5.2

Varity_R

0.11

gMVP

0.44

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over