13-37579312-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006475.3(POSTN):c.1708G>C(p.Gly570Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,447,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: POSTN NM_006475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POSTN	NM_006475.3	c.1708G>C	p.Gly570Arg	missense_variant	13/23	ENST00000379747.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POSTN	ENST00000379747.9	c.1708G>C	p.Gly570Arg	missense_variant	13/23	1	NM_006475.3	P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250962 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135662

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1447036 Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3 AN XY: 720768

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000760

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1708G>C (p.G570R) alteration is located in exon 13 (coding exon 13) of the POSTN gene. This alteration results from a G to C substitution at nucleotide position 1708, causing the glycine (G) at amino acid position 570 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.42
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Uncertain	2.7	M;.;M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.019	D;D;D;D;D;D
Sift4G	Benign	0.085	T;T;T;T;T;T
Polyphen		0.99	D;.;.;D;.;D
Vest4		0.91
MutPred		0.68		Gain of catalytic residue at L567 (P = 0);Gain of catalytic residue at L567 (P = 0);Gain of catalytic residue at L567 (P = 0);Gain of catalytic residue at L567 (P = 0);Gain of catalytic residue at L567 (P = 0);Gain of catalytic residue at L567 (P = 0);
MVP		0.95
MPC		0.71
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.60
gMVP		0.92

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

Other links and lift over

dbSNP: rs199954350; hg19: chr13-38153449;