13-37571407-A-T

Position:

• chr13-37571407-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006475.3(POSTN):​c.2141T>A​(p.Ile714Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POSTN NM_006475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38821644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2141T>A	p.Ile714Asn	missense_variant	18/23	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2141T>A	p.Ile714Asn	missense_variant	18/23	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

May 30, 2024

The c.2141T>A (p.I714N) alteration is located in exon 18 (coding exon 18) of the POSTN gene. This alteration results from a T to A substitution at nucleotide position 2141, causing the isoleucine (I) at amino acid position 714 to be replaced by an asparagine (N). 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	Benign	0.21
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	.;T;T;.
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.86	D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.4	.;.;L;.
MutationTaster	Benign	0.96	D;D;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.95	P;.;P;.
Vest4		0.59
MutPred		0.36		.;Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);.;
MVP		0.89
MPC		0.30
ClinPred		0.74	D
GERP RS		1.6
Varity_R		0.25
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-38145544; COSMIC: COSV101123292; COSMIC: COSV101123292;