chr13-37571432-C-G

Variant names:

• chr13-37571432-C-G
• rs142117360
• NM_006475.3:c.2116G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006475.3(POSTN):​c.2116G>C​(p.Glu706Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,608,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: POSTN NM_006475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28563917).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	NM_006475.3	MANE Select	c.2116G>C	p.Glu706Gln	missense	Exon 18 of 23	NP_006466.2	Q15063-1
	POSTN	NM_001286665.2		c.2035G>C	p.Glu679Gln	missense	Exon 17 of 22	NP_001273594.1	Q15063-5
	POSTN	NM_001330517.2		c.2116G>C	p.Glu706Gln	missense	Exon 18 of 22	NP_001317446.1	Q15063-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POSTN	ENST00000379747.9	TSL:1 MANE Select	c.2116G>C	p.Glu706Gln	missense	Exon 18 of 23	ENSP00000369071.4	Q15063-1
	POSTN	ENST00000379743.8	TSL:1	c.2035G>C	p.Glu679Gln	missense	Exon 17 of 22	ENSP00000369067.4	Q15063-5
	POSTN	ENST00000541179.5	TSL:1	c.2035G>C	p.Glu679Gln	missense	Exon 17 of 21	ENSP00000437959.1	Q15063-3

Frequencies

GnomAD3 genomes AF: 0.0000923 AC: 14 AN: 151704 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 250224 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.0000487 AC: 71 AN: 1456642 Hom.: 0 Cov.: 29 AF XY: 0.0000483 AC XY: 35 AN XY: 724894

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5742

European-Non Finnish (NFE) AF: 0.0000524 AC: 58 AN: 1107714

Other (OTH) AF: 0.000183 AC: 11 AN: 60212

GnomAD4 genome AF: 0.0000923 AC: 14 AN: 151704 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74114

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.000263 AC: 4 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67658

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000110

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.29	T
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.33	N
REVEL	Uncertain	0.42
Sift	Benign	0.14	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.27
MVP		0.92
MPC		0.59
ClinPred		0.16	T
GERP RS		5.5
Varity_R		0.27
gMVP		0.86
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs142117360; hg19: chr13-38145569;