9-27152345-C-T

Variant names:

• chr9-27152345-C-T
• rs664513
• NM_000459.5:c.53-5486C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000459.5(TEK):​c.53-5486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,212 control chromosomes in the GnomAD database, including 5,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5417 hom., cov: 31)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 2 publications found

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]

TEK Gene-Disease associations (from GenCC):

• multiple cutaneous and mucosal venous malformations

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• primary congenital glaucoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• TEK-related primary glaucoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• glaucoma 3, primary congenital, E

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• congenital glaucoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000459.5. 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
	TEK	NM_000459.5	MANE Select	c.53-5486C>T		intron	N/A	NP_000450.3	Q02763-1
	TEK	NM_001375475.1		c.53-5486C>T		intron	N/A	NP_001362404.1
	TEK	NM_001290077.2		c.53-5486C>T		intron	N/A	NP_001277006.2	Q02763-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEK	ENST00000380036.10	TSL:1 MANE Select	c.53-5486C>T		intron	N/A	ENSP00000369375.4	Q02763-1
	TEK	ENST00000519080.1	TSL:1	c.53-17150C>T		intron	N/A	ENSP00000428337.1	E5RIV9
	TEK	ENST00000923267.1		c.53-5486C>T		intron	N/A	ENSP00000593326.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39383 AN: 151094 Hom.: 5405 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39430 AN: 151212 Hom.: 5417 Cov.: 31 AF XY: 0.265 AC XY: 19537 AN XY: 73738

African (AFR) AF: 0.304 AC: 12491 AN: 41138

American (AMR) AF: 0.220 AC: 3348 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1659 AN: 5148

South Asian (SAS) AF: 0.518 AC: 2490 AN: 4804

European-Finnish (FIN) AF: 0.233 AC: 2392 AN: 10260

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15225 AN: 67880

Other (OTH) AF: 0.262 AC: 551 AN: 2102

Alfa AF: 0.199 Hom.: 1212

Bravo AF: 0.252

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.45
DANN	Benign	0.63
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs664513; hg19: chr9-27152343;