9-27109622-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000459.5(TEK):c.32G>A(p.Gly11Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEK NM_000459.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 4.70

Genes affected

TEK (HGNC:11724): (TEK receptor tyrosine kinase) This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEK	NM_000459.5	c.32G>A	p.Gly11Glu	missense_variant	1/23	ENST00000380036.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEK	ENST00000380036.10	c.32G>A	p.Gly11Glu	missense_variant	1/23	1	NM_000459.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Glaucoma 3, primary congenital, E Uncertain:2

Uncertain significance, no assertion criteria provided	research	Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	3billion	Jan 03, 2022	The variant is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.45	T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.65	D;D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.69	N;.;N;N;.
MutationTaster	Benign	0.96	D;D;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.18	N;.;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.25	T;.;D;D;T
Sift4G	Benign	0.55	T;T;T;T;T
Polyphen		0.99, 0.99	.;.;D;.;D
Vest4		0.61
MutPred		0.58		Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);
MVP		0.83
MPC		0.27
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.32
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr9-27109620;