chr13-37564552-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 0 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: 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2440G>C	p.Val814Leu	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>C	p.Val814Leu	missense_variant	Exon 22 of 23	1	NM_006475.3	ENSP00000369071.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1443112 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 718636

African (AFR) AF: 0.00 AC: 0 AN: 32948

American (AMR) AF: 0.0000227 AC: 1 AN: 43966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39386

South Asian (SAS) AF: 0.00 AC: 0 AN: 84768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097338

Other (OTH) AF: 0.00 AC: 0 AN: 59758

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	.;T;.;T;.;.
Eigen	Benign	0.034
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Uncertain	0.59	D
MutationAssessor	Benign	1.9	.;.;.;L;.;.
PhyloP100		1.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.45	N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.013	D;D;D;D;D;D
Sift4G	Uncertain	0.019	D;T;D;T;T;D
Polyphen		0.077	B;.;.;B;.;B
Vest4		0.21
MutPred		0.18		.;.;.;Gain of helix (P = 0.0425);.;.;
MVP		0.90
MPC		0.17
ClinPred		0.79	D
GERP RS		5.2
Varity_R		0.11
gMVP		0.44
Mutation Taster		=96/4	polymorphism

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;