13-37569335-A-G

Position:

• chr13-37569335-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006475.3(POSTN):​c.2396T>C​(p.Phe799Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00817 in 1,612,746 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (74 hom.)
• Consequence: POSTN NM_006475.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.02

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00763011).
• BP6: Variant 13-37569335-A-G is Benign according to our data. Variant chr13-37569335-A-G is described in ClinVar as [Benign]. Clinvar id is 782576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00828 (12096/1460694) while in subpopulation MID AF= 0.0444 (256/5760). AF 95% confidence interval is 0.04. There are 74 homozygotes in gnomad4_exome. There are 6077 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POSTN	NM_006475.3	c.2396T>C	p.Phe799Ser	missense_variant	21/23	ENST00000379747.9	NP_006466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POSTN	ENST00000379747.9	c.2396T>C	p.Phe799Ser	missense_variant	21/23	1	NM_006475.3	ENSP00000369071	P3

Frequencies

GnomAD3 genomes AF: 0.00711 AC: 1080 AN: 151934 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00983

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00766 AC: 1923 AN: 251150 Hom.: 13 AF XY: 0.00782 AC XY: 1062 AN XY: 135766

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00807

Gnomad ASJ exome AF: 0.0292

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00301

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.00947

Gnomad OTH exome AF: 0.0152

GnomAD4 exome AF: 0.00828 AC: 12096 AN: 1460694 Hom.: 74 Cov.: 30 AF XY: 0.00836 AC XY: 6077 AN XY: 726672

Gnomad4 AFR exome AF: 0.00248

Gnomad4 AMR exome AF: 0.00852

Gnomad4 ASJ exome AF: 0.0286

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00355

Gnomad4 FIN exome AF: 0.00358

Gnomad4 NFE exome AF: 0.00856

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.00708 AC: 1077 AN: 152052 Hom.: 5 Cov.: 32 AF XY: 0.00705 AC XY: 524 AN XY: 74358

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00983

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00984 Hom.: 22

Bravo AF: 0.00754

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0109 AC: 94

ExAC AF: 0.00698 AC: 848

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0123

EpiControl AF: 0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	POSTN: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 27, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T;.;.
Eigen	Benign	0.0034
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	T;T;T;T
MetaRNN	Benign	0.0076	T;T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.1	.;L;.;.
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.40	T;D;D;D
Sift4G	Benign	0.20	T;D;D;D
Polyphen		0.59, 0.87	.;P;.;P
Vest4		0.30
MVP		0.92
MPC		0.27
ClinPred		0.029	T
GERP RS		4.4
Varity_R		0.19
gMVP		0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs75157793; hg19: chr13-38143472;